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Nature’s Antimicrobial Arsenal: Non-Ribosomal Peptides from PGPB for Plant Pathogen Biocontrol

Academy of Biology and Biotechnology, Southern Federal University, Stachki 194/1, Rostov-on-Don 344090, Russia
Amity Institute of Environmental Sciences, Amity University, Sector 125, Noida 201301, India
Proteomics Lab., Division of Plant Biotechnology, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir (SKUAST-K), Shalimar, Srinagar 190025, India
Amity Institute of Environmental Toxicology Safety and Management, Amity University, Sector 125, Noida 201301, India
Author to whom correspondence should be addressed.
Fermentation 2023, 9(7), 597;
Submission received: 6 May 2023 / Revised: 19 June 2023 / Accepted: 20 June 2023 / Published: 26 June 2023
(This article belongs to the Section Microbial Metabolism, Physiology & Genetics)


Non-ribosomal peptides (NRPs) are a diverse group of bioactive compounds synthesized by microorganisms, and their antimicrobial properties make them ideal candidates for use as biocontrol agents against pathogens. Non-ribosomal peptides produced by Plant-Growth-Promoting Bacteria (PGPB) have gained interest for the biocontrol of plants’ bacterial and fungal pathogens. In this review, the structure and mode of action of NRPs, including their characterization and the characterization of NRP-producing microorganisms, are discussed. The use of NRPs in soilless agriculture and their potential as part of a sustainable plant disease control strategy are also highlighted. In addition, the review debates the commercial aspects of PGPB’s formulations and their potential as a biocontrol agent. Overall, this review emphasizes the importance of NRPs derived from PGPB in the biocontrol of plant pathogens and their potential to be used as an environmentally friendly and sustainable plant disease control strategy.

1. Introduction

Food is an essential requirement for human survival, and its production has been a matter of concern since prehistoric times. In the modern era, ensuring food security through sustainable strategies has become a major focus of the global research community [1]. Agriculture, as the main source of food, has undergone significant improvements in the last few decades, mainly emphasizing crop production and quality [2]. To meet the expanding demands of a growing population, advanced agricultural tools and improved crop varieties have also been introduced [3]. According to the Food and Agriculture Organization (FAO, 2021) of the United Nations Economic and Social Council, pests cause significant losses in global crop production, with estimates ranging from 20 to 40 per cent annually. Plant diseases alone cost the global economy around USD 220 billion each year, while invasive insects result in losses of around USD 70 billion. These losses have a significant impact on food security, economic stability, and the livelihoods of farmers worldwide [4].
When environmental factors impact a plant’s physiological processes, it can become vulnerable to infection, leading to changes in its structure, growth, and function, among other parameters [5]. Plant diseases are classified as infectious or non-infectious, depending on the nature of the disease-causing agents. Microorganisms such as bacteria, fungi, protozoa, and viruses can cause infectious diseases in plants. Bacteria, in particular, are ubiquitous and can be pathogenic to plants, animals, and humans. Many bacteria have genetic information contained in DNA molecules other than those of the bacterial chromosome, called plasmids, and although plasmid DNA does not carry the essential genetic information for the life of the bacterium, it does carry genes that give it new phenotypic properties and that, in some cases, are useful for their adaptation to growth in certain environments; for example, the b-lactamase enzymes that confer resistance to penicillins are encoded in plasmids [6]. It allows bacteria to acquire new traits rapidly, and it is also responsible for inducing antibiotic resistance among pathogenic bacteria [7].
In terms of evolution, fungi are much older than plants. The coexistence duration of plants and fungi can be compared to the evolutionary age of higher plants [8].
More than 90% of vascular plant species form some type of mycorrhizal association with fungi [9]. Mycorrhizal fungi form mutualistic associations with plant roots, providing nutrients and water to the plant in exchange for carbohydrates produced by the plant through photosynthesis [10].
This association is thought to have played a crucial role in the evolution of terrestrial plants, allowing them to colonize nutrient-poor soils and adapt to a terrestrial environment [11]. However, some fungi are also responsible for disturbing the balance between mutually beneficial relationships of plants and fungi by infecting the plant and acting as biotrophs, hemibiotrophs, or necrotrophs [12]. It has been observed that the majority of plant diseases are caused by soil-borne bacteria and fungi [13].
For the effective control of plant diseases caused by bacterial or fungal pathogens, the use of chemical agents has been popular. But, they do pose serious risks like resistance among pathogens, affecting non-target organisms, and entering the food chain to affect the ecosystem [14,15,16]. Primarily, the uncontrolled use of chemicals can permanently degrade soil quality. Furthermore, there are high economic costs associated with this approach, and several pesticide/insecticide-exposure-associated health problems can develop after they enter the food chain [15].
Therefore, it is imperative to devise efficacious and sustainable strategies to eliminate or curtail the use of synthetic and chemical disease control agents. In this regard, experts are focusing on microbial biocontrol as it offers environmentally friendly solutions [17,18]. Bacterial antagonists not only mitigate the deleterious effects of pathogens but also produce several organic compounds that are effective against a range of bacterial or fungal pathogens [19]. Of particular interest are microbial agents such as plant-growth-promoting bacteria (PGPB), which possess biological mechanisms to combat pathogenic growth [20]. These bacteria establish a symbiotic association with the plant, exerting beneficial effects by enhancing nutrient uptake, producing and releasing phytohormones, bolstering plant tolerance to environmental stressors, and suppressing plant diseases by adversely affecting phytopathogens [21]. Thus, these organisms are recognized as pivotal agents helpful in sustainable agriculture.
PGPBs colonize the rhizosphere and promote plant growth through various mechanisms and suppress plant diseases [22]. They are known to produce a variety of compounds that can be useful for the biocontrol of plant diseases [23,24] as well as combating the pollution load [25]. They can produce compounds with antimicrobial activity that inhibit the growth of pathogenic microorganisms. For example, many strains of Pseudomonas are reported to produce pyoluteorin, which has a broad-spectrum antimicrobial activity against a range of plant pathogens including fungi and bacteria. Pyoluteorin has been studied extensively as a potential biocontrol agent for managing plant diseases [26]. It has shown promise in field trials against a range of plant pathogens, including Fusarium [27], Rhizoctonia [28], and Phytophthora [29]. Pyoluteorin is considered a safe and environmentally friendly alternative to chemical pesticides for managing plant diseases, and further research is underway to explore its potential applications in agriculture. There are several other compounds such as hydrogen cyanide (HCN), and volatile organic compounds (VOCs) are secreted that can also deter potential pathogens [30].
In addition to several antimicrobial substances, non-ribosomal peptides (NRPs) have gained a lot of attention in the past decade. NRPs are a large group of structurally diverse natural products (Figure 1) that are synthesized by enzymes called non-ribosomal peptide synthetases (NRPSs) [31]. They are produced by certain bacteria, e.g., Bacilllus subtilis and Pseudomonas fluorescens are significantly useful for the biocontrol of plant diseases [32,33].
The objective of this review article is to explore the contribution of NRPs in the biocontrol of bacterial and fungal plant pathogens. Our study encompasses a comprehensive analysis of NRP synthesis, its mode of action, and characterization. In addition, we highlight the pivotal role that NRPs play in establishing sustainable plant disease control strategies and implementing biocontrol using PGPB in soilless agriculture. Furthermore, we deal with valuable insights into the commercial aspects of PGPB’s formulations, thereby providing a more comprehensive understanding of the subject matter.

2. Potential Non-Ribosomal Peptides for Biocontrol

Unlike ribosomal peptides, NRPs possess complex structures and exhibit a variety of biological activities. The structure of NRPs is highly diverse and complex. NRPs possess intricate and often non-linear architectures [34]. They are incorporated with a short stretch of amino acid building blocks including both proteinogenic and non-proteinogenic residues, which contribute to their structural variability [35]. NRPs can contain unique non-peptide bonds, such as ester, thioester, and amide linkages, formed through the actions of NRPSs. Many NRPs adopt cyclic structures, adding stability and rigidity to their conformation [36]. NRPs undergo modifications, such as oxidation, glycosylation, acylation, and phosphorylation, that further enhance their structural diversity [37]. Tailoring reactions mediated by specific enzymes introduce additional modifications and functional groups. The combination of these factors results in the remarkable diversity of NRPs, allowing them to exhibit a range of biological activities and making them attractive candidates for drug discovery and therapeutic applications [38]. Among the various NRPs, iturin, surfactin, and fengycin are some notable examples (Figure 2).
  • Iturin
Iturin is a cyclic lipopeptide compound that belongs to the family of secondary metabolites known as iturins. It is a kind of cyclic lipopeptide (CLP) produced by Bacillus subtilis and other closely related bacteria [32]. Many strains of B. subtilis are known to produce iturin and it has a broad-spectrum inhibitory effect on many plants’ pathogenic fungi and bacteria [39]. Many different members of the iturin family have common structures, but they also have their characteristic structures. The most important representatives of the iturin family are iturin A, C, D, and E, and the mycobacterium subtilisin and bacteriomycin variants (D, F, L) [40]. In nature, iturin A consists of eight variants, each named Iturin A1-A8 [41]. These isomers are often produced as mixtures with molecular weights ranging from 1029 to 1084 Da [42]. The production of iturin by Bacillus subtilis is considered a significant trait that contributes to its biocontrol and plant-growth-promoting properties [43]. Iturin has garnered considerable attention due to its diverse biological activities and potential applications in the agriculture and pharmaceutical industries [39].
The structure of iturin consists of a cyclic peptide ring linked to a fatty acid chain [44]. The peptide ring is composed of seven amino acids, with the amino acid sequence varying among different iturin variants. The fatty acid chain, typically consisting of 14 to 17 carbon atoms, is responsible for the amphiphilic nature of iturin, enabling it to interact with both hydrophobic and hydrophilic environments [45]. The specific structure of iturin contributes to its various bioactive properties, including antifungal, antibacterial, and surfactant activities [46].
The genes encoding iturin are typically found within the genome of bacteria belonging to the Bacillus genus. Specifically, the genes responsible for the biosynthesis of iturin are part of the non-ribosomal peptide synthetase (NRPS) gene cluster. NRPS genes are involved in the production of various peptide-based compounds, including iturin. Iturins do vary slightly between different strains of Bacillus and are biosynthesized by a cluster of genes including ituA, ituB, ituC, and ituD [47]. These genes encode the enzymes necessary for the assembly of the iturin peptide and the subsequent modifications that occur during its biosynthesis [48]. The arrangement and organization of the iturin-encoding gene clusters vary within the strains and species [49].
The mode of action of iturin involves its interaction with cellular membranes, leading to disruption and subsequent cell death [50]. Iturin’s amphiphilic nature allows it to insert into the lipid bilayer of cell membranes. The hydrophobic fatty acid chain of iturin embeds into the hydrophobic region of the lipid bilayer, while the cyclic peptide ring remains in the aqueous environment [51]. Once inserted, iturin causes changes in the membrane’s physical properties, including fluidity and permeability. Iturin molecules aggregate and form channels or pores within the membrane, resulting in the leakage of ions, metabolites, and other essential components from the cell. This disruption of the membrane’s integrity leads to cell lysis and ultimately the death of the target organism [52]. The membrane-disrupting activity of iturin is primarily attributed to its ability to interact with ergosterol, a sterol found in the cell membranes of fungi, or with other membrane components in bacteria. Iturin molecules preferentially bind to ergosterol or certain lipids present in bacterial membranes, disrupting their normal function and compromising cell viability [53]. Iturin A has been reported to severely damage the plasma membranes by forming a large pore in the cell of Fusarium graminearum at MIC = 5 µg/mL and to successfully inhibit the hyphal growth [54]. Iturin A has also been reported to stimulate oxidative stress, leading to mitochondria damage and the eventual destruction of the pathogen cell [55].
Iturin’s potential applications extend beyond agriculture and encompass areas such as pharmaceuticals and cosmetics. Its surfactant properties make it a valuable ingredient in various formulations, including detergents and emulsifiers. The ability of iturin to promote plant growth and induce systemic resistance (IRS) in plants has led to its utilization as a biocontrol agent in integrated pest management strategies. In inference, iturin is a cyclic lipopeptide produced mostly by Bacillus subtilis, with diverse biological activities and potential applications. Its structure, detection methods, and characterization techniques enable scientists to explore its properties and understand its mode of action. By further investigating iturin’s potential and optimizing its production, it may hold promise for addressing challenges in agriculture, healthcare, and other industries.
Surfactin, a well-studied biosurfactant, is produced by various Bacillus species such as B. amyloliquefaciens, B. subtilis, and B. pumilus [56]. It possesses unique physicochemical properties due to its amphiphilic structure, enabling foaming, emulsifying, hydrophobic surface modification, and chelation abilities [57]. Its structure comprises a peptide loop of seven amino acids and a variable-length β-hydroxy fatty acid chain. The hydrophilic characteristic and negative charge of the peptide loop, consisting of glutamic acid and aspartic acid residues, contrast with the major hydrophobic domain formed by the valine residue facing the fatty acid chain [58]. Surfactin exhibits hydrophobic interactions within micelles below the critical micellar concentrations (CMCs), allowing the fatty acid tail to extend freely into the solution [59].
Notably, surfactin acts as a broad-spectrum antibiotic with detergent-like activity, increasing the permeability of cell membranes in bacteria irrespective of their Gram stain classification [60]. Its minimum inhibitory concentration (MIC) ranges from 12 to 50 μg/mL [61]. Additionally, surfactin has gained attention for its antifungal properties, particularly against phytopathogenic fungi such as Fusarium, Lasiodiplodia, Colletotrichum, Botryosphaeria, Aspergillus, and Penicillium [62].
Fengycin is a lipopeptide compound produced by certain strains of Bacillus subtilis, a common soil bacterium. It belongs to the cyclic lipopeptide family and is known for its biocontrol activity against plant pathogens [63,64]. Fengycin has a complex structure consisting of a cyclic heptapeptide ring linked to a β-hydroxy fatty acid chain. This unique structure contributes to its biological activities [65].
The major source of fengycin is Bacillus subtilis, a Gram-positive bacterium widely distributed in the environment, including the soil, water, and plant rhizosphere. Several strains of Bacillus subtilis, as well as genus Bacillus, e.g., B. subtilis F29-3, and B. amyloliquefaciens MEP218, are known to produce fengycin [66,67]. These strains can colonize plant roots and establish a beneficial relationship with plants, promoting growth and protecting them from pathogenic infections [68,69,70].
Fengycin demonstrates strong biocontrol activity against a variety of plant pathogens, particularly fungal pathogens [71]. It acts by inhibiting the growth and development of pathogenic fungi, thereby protecting plants from diseases. Fengycin disrupts the integrity of fungal cell membranes, leading to their lysis and subsequent death [72]. It is effective against several fungal genera, including Fusarium, Alternaria, and Botrytis, which are notorious for causing devastating crop diseases [73].
The biocontrol activity of fengycin is of great interest in the field of agriculture as it provides an eco-friendly and sustainable approach to disease management [74,75]. By making optimal utilization of fengycin-producing strains of Bacillus, the dependency on chemical fungicides can be reduced, which often have harmful effects on the environment and can contribute to the development of pesticide resistance in pathogens [15]. Its selectivity toward fungal pathogens and its minimal impact on beneficial organisms make it a valuable tool for integrated pest management strategies [76].
Apart from these three, several other NRPs are discussed in the application section of the manuscript.

3. Synthesis, Mode of Action, and Characterization

  • Synthesis of NRPs
Non-ribosomal peptides are small peptides that are synthesized by non-ribosomal peptide synthetases (NRPSs). Unlike other peptides, NRPs are not dependent on messenger RNA translation by ribosome. The synthesis of NRPs is mediated by NRPS biosynthetic gene clusters (BGCs), which possess specific domains generally referred to as modules. These modules contribute to specific amino acids and modify the growing peptide, resulting in the generation of short peptide structures with diverse chemical modifications, including cyclic, branched, and non-proteinogenic amino acids [77]. Additionally, oxidation, reduction, and dehydration reactions can also occur during NRP synthesis.
The NRPSs are exclusive to one type of peptide compound, and the modules within NRPS BGCs usually have an initiation module, elongation module, and termination module (Figure 3). The initiation module involves formylation or N-methylation, adenylation, thiolation, and peptide carrier proteins with attached 4’-phospho-pantetheine. The elongation modules include condensation to form the amide bond, cyclization into thiazoline or oxazolines, N-methylation, adenylation, thiolation, and epimerization into D-amino acids. Lastly, the termination module involves termination by a thioesterase or reduction to a terminal aldehyde or alcohol [78,79]. The final peptide product is frequently subject to modifications, such as glycosylation, acylation, halogenation, or hydroxylation, which are often carried out by enzymes associated with the synthetase complex [80]. These enzymes are typically encoded within the same operons or gene clusters [81]. Non-modular NRPS enzymes are more prevalent in bacterial systems, where they are often arranged in clusters [77]. These nonmodular NRPS enzymes consist of one or two A-PCP-C modules or may lack complete A-PCP-C modules and instead have a single A-domain or an A-PCP unit followed by a variety of C-terminal domains. However, such multiple repeating modules are commonly referred to as A-PCP-C domains. These multi-modular NRPSs are commonly found in fungal genomes, where these modules that are involved in peptide assembly are connected within a single enzyme [82].
In bacterial systems, biosynthesis can be performed by mono- or bi-modular NRPSs. These proteins interact with other NRPS proteins to activate amino acids and transfer the activated substrate to either a C domain in the same NRPS or a different NRPS [83]. This type of biosynthesis is known as nonlinear biosynthesis [84]. The distribution of mono/bi modular NRPS subfamilies across taxonomic groups suggests that these structures may have originated in ancient times, potentially predating the divergence of eubacteria and fungi. NRPSs can also be fused to a polyketide synthase (PKS) unit, creating a single polypeptide that combines both types of synthetases [85].
Several PGPB and also some fungi have been reported to produce a wide range of NRPs such as surfactin, iturin, fengycin, and polymyxin that have been associated with diverse biocontrol activity against a number of plant pathogens [86]. The U.S. Food and Drug Administration (FDA) and the U.S. Environmental Protection Agency have authorized their use as commercial applications (EPA) [82].
Mode of action
NRPs have been found to exhibit diverse mechanisms of action against bacterial pathogens, making them valuable therapeutic agents for the study of bacterial diseases among plants. The most common method of action that NRP follows is action on the cell wall and its synthesis machinery. It is one of the mechanisms of action of NRPs against bacteria that inhibits cell wall synthesis. NRPs such as vancomycin, daptomycin, and bacitracin are known to inhibit the biosynthesis of bacterial cell walls by targeting key enzymes involved in peptidoglycan synthesis [87,88]. These NRPs bind to specific targets in the cell wall synthesis pathway, leading to the inhibition of bacterial growth and cell division.
Vancomycin is a glycopeptide NRP produced by a soil bacterium Amycolatopsis orientalis; it binds to the D-alanyl-D-alanine terminus of the peptidoglycan precursor, thereby inhibiting its incorporation into the growing cell wall. The binding of vancomycin to the peptidoglycan precursor prevents the formation of cross-links between peptidoglycan chains, leading to the inhibition of cell wall synthesis and bacterial growth [89]. Similarly, daptomycin is a lipopeptide antibiotic that binds to the bacterial membrane and causes depolarization of the membrane potential, leading to the disruption of membrane function and cell death [90]. Bacitracin is a cyclic peptide antibiotic that inhibits the dephosphorylation of the peptidoglycan precursor, leading to the accumulation of the precursor and the inhibition of cell wall synthesis [91]. Bacitracin binds to the undecaprenyl-pyrophosphate carrier molecule, which is responsible for the transport of the peptidoglycan precursor across the cell membrane [92]. The binding of bacitracin to the carrier molecule prevents the transport of the precursor, leading to the inhibition of cell wall synthesis and bacterial growth. Fengycin is also one of the potent antimicrobial substances. C16-Fengycin has been reported to be involved in both cell wall destruction and the accumulation of reactive oxygen species (ROS), which may activate the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase (HOG-MAPK) pathway [93]. Fengycin BS155 affects the mitochondrial membrane potential (MMP), elevates the ROS bursts, and simultaneously negatively affects the ROS-scavenging enzymes [72].
Another mechanism by which NRPs act on the pathogen is the disruption of membrane function. NRPs such as polymyxins and gramicidin are known to disrupt the structure and function of bacterial cell membranes. Polymyxins are a group of CLP antibiotics that interact with the lipid components of the bacterial cell membrane, leading to the formation of ion channels and pore structures that disrupt the membrane’s integrity and lead to cell death [94]. Polymyxins have been shown to bind to the lipid A component of the bacterial cell membrane, leading to the disruption of the membrane structure and the release of intracellular contents [95]. Daptomycin has also been shown to bind to the bacterial cell membrane and form channels that allow the influx of ions, leading to the disruption of the membrane potential and the loss of membrane integrity [96].
Gramicidin is a CLP compound that forms channels in the bacterial cell membrane, leading to the disruption of membrane function and cell death. Gramicidin has been shown to bind to specific lipid components of the bacterial cell membrane, leading to the formation of ion channels and the influx of ions, which disrupts the membrane potential and leads to the loss of membrane integrity [97]. For example, gramicidin A (gA) forms a channel in lipid membranes, which allows H+ ions conduction through the lipid bilayer of pathogens [98]. Surfactin also exhibits a range of antimicrobial mechanisms. It can cause the disintegration of cell membranes or osmotic pressure imbalance, leading to the leakage and lysis of lipid membranes [58].
NRPs are also reported to interfere with nucleic acid integrity. Bacillomycin D, which is a potent antifungal compound and effectively combats Aspergillus ochraceus (a common fungal contaminant in food samples), affects the hyphal distortion and sporular disruption in A. ochraceus, leading to decreased fungal growth. A study has reported that bacillomycin D binds to the DNA of A. ochraceus and affects its integrity, which can ultimately affect its growth. The study also found that bacillomycin D caused breaks in A. ochraceus DNA and inhibited its repair mechanisms, leading to cell death [99]. Fengycin BS155 is reported to induce chromatin condensation, resulting in an upregulation of DNA-repair-related protein expression and cleavage of poly (ADP-ribose) polymerase (PARP) [72].
NRPs have also been found to modulate bacterial virulence by affecting key virulence factors such as quorum sensing and biofilm formation [100]. NRPs such as agrimophol and fengycin have been shown to inhibit quorum sensing in Gram-positive bacteria, leading to the inhibition of virulence factor production and the attenuation of bacterial virulence [101].
NRPs exhibit diverse mechanisms of action against bacterial pathogens. NRPs can inhibit cell wall synthesis, disrupt membrane function, interfere with nucleic acid integrity, affect protein synthesis, and modulate bacterial virulence. The unique mechanisms of action of NRPs make them potential agents for the biocontrol of bacterial and fungal pathogens of plants.
The modular structure of NRPs allows for the incorporation of various amino acids and other functional groups, thereby producing a range of chemical structures and biological activities. The characterization of NRPs is important for understanding their biological function, as well as for the discovery of new natural compounds with potential antagonistic activity and promising scope in the biocontrol of plant pathogens.
Bioassays are an important and primary approach for the identification of NRPs. It involves the testing of NRPs for biological activity, such as antimicrobial (for biocontrol) or anticancer activity (many NRPs have reported anti-cancer activities). The two most common bioassays that can be used are disk diffusion assays and broth dilution assays. However, further mass culturing for harvesting possible NRPs is carried out.
The second step in the characterization of NRPs is the isolation and purification of metabolites from the selected potential microbes. NRPs can be obtained from mass culture broths of microorganisms by various extraction techniques, such as solvent extraction [102,102], solid-phase extraction [103], and liquid–liquid extraction. After extraction, the crude extract is subjected to a series of purification steps, such as column chromatography, high-performance liquid chromatography (HPLC), and preparative thin-layer chromatography (TLC), to obtain pure NRPs [104]. The purity of the NRP is determined by analytical HPLC or TLC.
  • Mass spectrometry (MS) is a powerful technique for the analysis of NRPs [105]. MS allows for the determination of the mass-to-charge ratio (m/z) of the NRP and its fragments [106]. This information helps identify the exact chemical structure of the NRP, as well as to determine its molecular weight and the presence of various functional groups [107]. Several types of MS techniques can be used for the analysis of NRPs, including matrix-assisted laser desorption/ionization (MALDI-TOF) MS [108], electrospray ionization (ESI) MS [109], and tandem mass spectrometry (MS/MS) [110].
MALDI MS is a soft ionization technique that is particularly useful for the analysis of large biomolecules, such as NRPs. In MALDI MS, the sample is mixed with a matrix material and deposited on a target plate. The sample is then irradiated with a laser, which causes the matrix to vaporize and ionize the sample molecules. The resulting ions are then detected and analyzed [111]. Electron spray ionization (ESI) MS is another soft ionization technique that is commonly used for the analysis of NRPs. In ESI MS, the sample is ionized in a solution containing a volatile buffer and injected into a mass spectrometer. The sample is then subjected to an electric field, which causes the sample ions to be generated and detected [112]. MS/MS can be performed using various fragmentation methods, such as collision-induced dissociation (CID) [113] and electron transfer dissociation (ETD) [109].
  • The use of nuclear magnetic resonance (NMR) spectroscopy has also been reported in NMR characterization; however, it can be tedious, error-prone, and require substantial quantities of purified material [114]. This can be especially problematic since NRPs are often produced by microorganisms that are difficult to cultivate, making it challenging to obtain enough material for NMR-based sequencing [115]. As a solution, a new nanomolar scale approach to NRP sequencing is needed. A recent study has claimed to identify three compounds, keanumycins A-C, from Pseudomonas sp. QS1027 using NMR that is found to have significant potential against phytopathogen Botrytis cinerea [116].
  • X-ray crystallography has also been employed often for the analysis of NRPs that have complex three-dimensional structures [117,118] or are difficult to analyze using other techniques [119]. However, the technique requires the NRP to be crystallized, which can be challenging for some NRPs [35].
  • Genome mining is a relatively new approach to the identification of NRPs. It involves the analysis of the genome sequence of microorganisms to identify BGCs for NRPSs and other biosynthetic enzymes [120]. It can also be used to predict the chemical structures of NRPs based on the presence of specific biosynthetic genes. There are several computational tools available for genome mining, such as antiSMASH and NRPSpredictor [121]. These tools can be used to predict the chemical structures of NRPs, as well as to identify potential new NRPs.
To sum up, the characterization of NRPs from bacteria or fungi is a complex and multidisciplinary process that requires a combination of analytical techniques (Figure 4). Isolation and purification, bioassays, mass spectrometry, nuclear magnetic resonance spectroscopy, X-ray crystallography, and genome mining are all important tools for the characterization of NRPs.

4. Application of NRPs in Sustainable Agriculture

The NRPs produced by PGPB can offer the biocontrol of plant pathogens through a variety of mechanisms. One of the primary mechanisms is directly inhibiting the growth and development of plant pathogens. NRPs can do this by interfering with key cellular processes such as DNA replication, protein synthesis, and cell wall synthesis in the target pathogen [122]. In addition to their direct effects on plant pathogens, NRPs can also indirectly promote plant health and defense against pathogens. For example, some NRPs can exhibit IRS in plants, e.g., surfactin, bacillomycin, and fengycin provided IRS among Arabidopsis plantlets against P. syringae pv. tomato (Pst DC3000) and Botrytis cinerea [123], Priming with such PGPR could certainly be more effective in mitigating the pathogen attacks [124]. NRPs produced by PGPBs make them promising candidates for the biocontrol of plant pathogens, with the potential to reduce the reliance on traditional chemical pesticides and antimicrobial agents and promote more sustainable agricultural practices.
Some of the NRPs, like surfactin and iturin, are potential plant disease biocontrol agents as they exhibit antimicrobial properties, and some other NRPs such as daptomycin and polymyxin are used as antibiotics to handle animal and human diseases that are caused by pathogenic bacteria. [24]
The potential benefit of using NRPs is that they may have a lower risk of causing resistance compared to traditional pesticides. Several plant pathogens have developed resistance to chemical pesticides over time, making them less effective for disease control [125]. NRPs, however, have a more complex structure and mode of action compared to traditional pesticides, which may make it more difficult for pathogens to develop resistance [126]. Apart from this, NRPs may be more environmentally friendly compared to traditional pesticides [127]. Many traditional pesticides certainly have negative impacts on non-target organisms and the environment. NRPs, on the other hand, are typically produced by naturally occurring microorganisms and may have a lower toxicity to non-target organisms [122].
In this section, we discuss the NRPs for controlling bacterial and fungal plant pathogens.

4.1. Impact on Bacterial Pathogens

NRPs are produced by a variety of bacteria and fungi, and several NRP molecules have strong antimicrobial properties against bacterial and fungal pathogens of plants. NRPs can be highly specific in their activity, targeting specific bacterial species or strains, making them a promising alternative to broad-spectrum antibiotics that are susceptible to gaining antibiotic resistance [126]. Studies have demonstrated the effectiveness of NRPs in controlling a range of bacterial pathogens of the plant, viz., several strains of Pectobacterium, Pseudomonas, Ralstonia, and Xanthomonas [24]. For example, bacteria of the genus Burkholderia inhabit diverse ecological niches and play important roles in the environment through the secretion of various secondary metabolites including modular NRPs and polyketides (PKs). These metabolites represent a class of broadly biomedical and bioregulatory important natural products, such as antibiotics, siderophores, anticancer agents, and biopesticides, which can protect ecological niches from competitors and are considered a new source that can be used to promote plant growth [128].
Bacillus genera are one of the leading genera that have been widely studied for the production of potential NRPs. The major bioactive molecules the Bacillus genera have been reported to synthesize are NRPs/lipopeptides, polyketide compounds, bacteriocins, and siderophores [32,129]. Bacillus lipopeptides have a highly complex biosynthetic mechanism activated via NRPSs. It is a large enzyme complex with a modular structure with each module responsible for the incorporation of a specific amino acid. In Bacillus subtilis strains, approximately 4–5% of the total genome is dedicated to the synthesis of secondary metabolites having the potential to generate over 20 structurally distinct antimicrobial compounds [32]. Many species of the Pseudomonas genus are also potent biocontrol agents that can produce cyclic lipopeptides (CLPs) along with quinolones, siderophores, phenazines, phloroglucinol, hydrogen cyanide, and rhamnolipids. There are varieties and differences in secondary metabolite production even within the same Pseudomonas strains [130].
A list of such NRPs is provided that demonstrates the biocontrol of bacterial pathogens of the plant in Table 1.

4.2. Impact on Fungal Pathogens

Phytopathogenic fungi are amongst the most common infectious agents in plants and one of the principal plant infections that cause significant monetary and production losses. Plant pathogenic fungi have been the most diverse and deadly class of economic and ecological dangers throughout the history of agriculture [140]. Many secondary metabolites produced by microorganisms have been reported to act as antifungal agents against phytopathogenic fungi [141,142,143].
However, some strains of Bacillus and Pseudomonas produce short peptide compounds that are synthesized non-ribosomally such as bacilysin, mycobacillin, bacillomycin, mycosubtilin, iturins, fengycins, and surfactins that have antimicrobial properties [32,34]. These NRP compounds are antagonistic to numerous additional plant pathogenic fungi, including Fusarium. graminearum, F. oxysporum, F. solani, and Rhizoctonia solani [54,144].
NRPs like surfactin produced by Bacillus have exhibited potent antifungal action against Trichoderma reesei, T. atroviride, F. moniliforme, F. oxysporum, and F. solani [145,146]. Similarly, mycosubtilin produced by B. subtilis has shown a significant inhibition potential of Pythium infection in tomato seedlings [147]. Numerous research studies have documented the impact of NRPs on the biocontrol of fungal pathogens. However, this article aims to emphasize the latest findings regarding the use of NRPs as a biocontrol measure against pathogenic fungi. To facilitate understanding, a table is included below to provide additional information (Table 2). It highlights the compounds with their source, method of characterization, and antagonism to the pathogen with appropriate citations. This table includes several recent investigations worth highlighting.

4.3. Biocontrol in Soilless Agriculture

Soilless agriculture has gained significant attention over the years due to its numerous advantages over traditional soil-based agriculture, including the better control over nutrient uptake and plant growth, and reduced disease incidence. However, soilless agriculture is also associated with a higher risk of plant disease, especially when compared to conventional soil-based agriculture. In response, the use of PGPBs has emerged as a viable solution to promote plant growth and control disease incidence in soilless agriculture. NRPs have been identified as effective biocontrol agents, with the potential to reduce plant disease incidence in soilless agriculture. NRPs have been shown to play an important role in plant disease control. In soilless agriculture, plants are grown in a sterile environment, which makes them more susceptible to disease. Additionally, the use of hydroponic systems can lead to the build-up of pathogens, as the recirculating nutrient solution can harbor pathogens that can infect plants.
In this perspective, the use of NRPs producing PGPB can provide an effective means of controlling plant diseases in soilless agriculture. By inhibiting the growth of plant pathogens, NRPs can reduce the incidence of disease, thus promoting plant growth and increasing yield. Additionally, NRPs may also enhance plant defenses against pathogens, further reducing the risk of disease. Recent research studies have shown successful implementations of PGPB in hydroponics, as demonstrated in Table 3.
The PGPB’s application can also enhance plant growth by promoting optimal root growth and increasing biomass, chlorophyll content, and leaf surface area. Additionally, it has been found to confer tolerance to both abiotic and biotic stress factors, as well as improve nutrient uptake [86].
The colonization of PGPB is more effective in soil systems compared to hydroponic systems [87,88]. While soilless agriculture has its benefits, such as the ability to control the nutrient supply and minimize the presence of pests and diseases, there are certain limitations. For instance, the substrates used in soilless systems to support roots are not as versatile as soil. Moreover, soil also hosts a variety of beneficial organisms, such as nematodes and earthworms, which aid in the cycling of nutrients and promote advanced colonization, leading to better plant growth. In soilless systems, nutrient availability mainly relies on external sources like commercial nutrients. However, nutrients alone cannot provide optimal growth for plants, which is why PGPB plays a crucial role in such a system [89]. The NRPs directly help in the biocontrol of antibacterial and antifungal properties (Table 4) and also act as a biostimulator by ensuring the presence of compounds such as antioxidants and enzymes, aiding in plant growth [170]. Siderophores and plant hormones are also significantly helpful in plant growth and optimal health [171]. PGPB metabolites also indirectly contribute to plant growth [172].
Numerous studies have been conducted on PGPB in soil systems, and the results have been promising, which highlights their potential benefits in soilless farming as well [173]. Hence, its application in such systems is an exciting opportunity for promoting plant growth and deserves further investigation.
Table 4. Application of various plant-growth-promoting bacteria on different plants in soilless culture.
Table 4. Application of various plant-growth-promoting bacteria on different plants in soilless culture.
S. NoType of PGPBMediaCropsReferences
1.Bacillus sp, Halobacillus sp., B.gibsonii, Staphylococcus succinus, Zhihengliuella halotolerans, Oceanobacillus oncorhynchi, Exiguobacterium aurantiacum, B.atrophaeus, Zhihengliuella sp., Halomonas sp., Virgibacillus picturae, Oceanobacillus sp., and Thalassobacillus spHydroponicTriticum aestivum[174]
2.Bacillus amyloliquefaciens, B. brevis, B. circulans, B. coagulans, B. firmus, B. halodenitrificans, B. laterosporus, B. licheniformis, B. megaterium, B. mycoides, B. pasteurii, B. subtilis, and Paenibacillus polymyxaHydroponic floating systemLactuca sativa L. var. Crispa[175]
3.Enterobacter hormoecheiHydroponicsCucumis sativus[176]
4.Acinetobacter calcoaceticusHydroponicsLactuca sativa[177]
5.BFD160 Enterobacter asburiae, TFD26 P. koreensis, and BFS112 P. liniiSoilless culture comprising rock wool blocks placed in plastic pots containing perlite and peat (1:1)Cucumis melo L[178]
6.Pseudarthrobactr chlorophenolicus BF2P4-5Cocopeat mediaS. lycopersicum[179]
7.Flavobacterium crocinum HYN0056TSoilless culture comprising cocopeat (51.5%), peat moss (10%), Vermiculite (13%), perlite (15%), zeolite (10%), humic acid (0.1%), fertilizer (0.4%)Arabidopsis thaliana[180]
8.Pantoea dispersa, Pantoea ananatis, Burkholderia arboris, Burkholderia pyrrocinia, and Burkholderia pyrrociniaCocopeat substrateSolanum melongena[181]
9.B. megaterium TV-91C, Pantoea agglomerans RK-92, and B. subtilis TV17CPeatBrassica oleracea var. capitata ‘Yalova1’[182]
10.B. amyloliquefaciens, B. subtilis, B. pumilus, and B. sphaericusPeat mossCucurbita pepo and
S. lycopersicum
11.Rhizobacterium, B. subtilisPerliteLactuca sativa ‘Partavousi’[70]
12.Bacillus sp.HydroponicsZea Mays[184]
13.P. pseudoalcaligenes and Bacillus subtilisHydroponicsGlycine max L.[185]
14.Sinorhizobium meliloti and P. fluorescenceSoilless media containing sand and sterile perlite (v/v, 2:1)Medicago sativa L.[186]

4.4. Future Prospective

NRP-producing bacteria have been isolated from soil, the rhizosphere, and plant tissues. They are known to possess several biological activities, including antimicrobial, antifungal, and antiviral properties. A major and diverse potential application of NRP-producing bacteria in sustainable agriculture is as biocontrol agents for plant pathogens. B. subtilis and Pseudomonas have been popularly studied bacteria for biocontrol, as they produce effective NRPs against a range of plant pathogens. The production of NRPs by bacteria can be influenced by various factors, including bacterial strain, growth conditions, and the presence of other microorganisms in the environment. They can produce NRPs that can inhibit the growth of plant pathogenic fungi and bacteria. This is effective in controlling plant diseases and reducing the use of chemical pesticides. NRPs are also specific to certain plant pathogens and can inhibit their growth and spread.
In addition, NRP-producing PGPB is also conferred with plant-growth-promoting traits that enable nutrient solubilization, phytohormones, and the development of root structure architecture. They are also capable of degrading xenobiotic compounds such as persistent organic pollutants (PCBs, PAHs, and pesticides), heavy metal remediation, and improving plant resistance to biotic and abiotic stresses. The PGPBs enable IRS among the plants and are also significantly crucial for plant health and enhanced crop productivity. The PGPB play a significant role in soil health and the ecosystem, important for sustainable agriculture as the production of NRPs and subsequent pathogen control can influence the composition and diversity of soil microbial communities, which have positive impacts on overall soil health and nutrient cycling.
However, there are challenges associated with the use of NRP-producing bacteria in sustainable agriculture. One challenge is cost-effectiveness, as microbial preparation for biocontrol can be expensive and time-consuming. Further requirements of genetically engineered microorganisms for enhanced biocontrol can also negatively affect cost-effectiveness. They also raise concerns about potential risks to the environment and human health without appropriate risk assessment studies and approvals.
The development of effective and efficient methods for the large-scale production and application of NRPs/NRP-producing PGPBs to plants and the production of NRPs by bacteria can be influenced by various environmental factors.
NRPs produced by PGPB have potential applications in sustainable agriculture for biocontrol agents, plant-growth-promoting agents, and to improve soil health. However, the challenges associated with their production and delivery must be addressed to ensure their effectiveness and safety in agricultural practices.

4.5. Commercial Aspects of PGPB Formulations for Biocontrol Strategies

PGPB formulations are faster becoming popular in agriculture as a means of improving plant growth, health, and yield. These formulations contain live PGPBs that can colonize the roots of plants and promote their growth by improving nutrient uptake, reducing stress, and suppressing pathogens. However, as with any commercial product, various aspects need to be considered in the development and marketing of PGPB formulations. There are many examples of PGPB formulations that have been successfully developed and commercialized (Table 5). Some of them are listed below:
An important aspect of the commercialization of PGPB formulations is the selection of the bacterial strains to be incorporated into the product. Several strains of PGPBs have shown excellent results in terms of plant growth and yield; still, it is crucial to assess and recognize the most effective ones for the crops and soil application where the product will be used. It requires extensive research and testing for the potential of PGPBs to control plant pathogens along with other plant-growth-promoting traits such as nitrogen fixation, nutrient acquisition, and phytohormones production. Field trials are far more crucial than evaluating the effectiveness under actual environmental conditions and determining the optimal application rates and methods.
Another important aspect of such formulations is the preparation itself. For the PGPB to be effective and formulation to be successful, it must be devised in a way that allows PGPBs to survive storage, transportation, and application in varying environmental conditions. This can be achieved through various means, such as encapsulation or blending in compatible matrices, or by incorporating the PGPB into a carrier such as vermiculite or peat moss. The formulation must also be compatible with the intended application method, whether that be through seed treatment, soil application, or foliar spray.
The production and distribution of PGPB formulations also involve an understanding of various commercial aspects, viz., quality control, regulation/policy framework, and marketing. Quality control is essential to ensure that the PGPB are viable and effective throughout the product’s shelf life, and this requires rigorous testing and monitoring of production processes.
Regulation is another important criterion, as PGPB formulations may be subject to different regulations in different countries or regions. This includes compliance with regulations governing the use of genetically modified organisms (GMOs) or the use of microorganisms in agriculture.
Marketing is a decisive aspect of PGPB formulations, as successful marketing can help to increase the adoption and sales of the product. This entails a strong sense of the target market, including the crops and regions where the product will be most effective, as well as the benefits and limitations of the product. Effective marketing can include advertising, trade shows, and other promotional activities, as well as partnerships with distributors or retailers to increase product availability and visibility.
To infer, the commercial aspects of PGPB’s formulations are complex and require careful consideration of many factors, including its selection, formulation, production, regulation, and marketing. However, with careful planning and execution, PGPB formulations have the potential to revolutionize agriculture by improving plant growth and health in a sustainable and environmentally friendly manner.

5. Conclusions

It is evident that NRPs are promising candidates for biocontrol agents against bacterial and fungal pathogens. The structural diversity among NRPs and their mode of action make them significantly effective against several plant pathogens, including those that have developed resistance to conventional chemical treatments and antimicrobial agents. The growing concern of sustainable agriculture has led to many front advances in research on NRPs and its prospecting. Subsequently, the methods of characterization of NRPs have been rapidly advancing, making it easier to identify and optimize their bioactivity. Moreover, the application of PGPBs in soilless agriculture has shown great potential in enhancing plant growth and productivity. Hence, prospecting them for biocontrol in soilless agriculture is correspondingly promising.
The forthcoming NRPs in biocontrol are highly promising, with increasing interest from the commercial sector for their use in agriculture. However, more research is still needed to fully understand the mechanisms of action of NRPs and to optimize their formulations, production, and delivery. Overall, NRPs represent a promising avenue for the sustainable and effective biocontrol of plant pathogens, and further research into their potential is substantially realistic in sustainable agriculture.

Author Contributions

Conceptualization, A.R. and E.V.P.; methodology, E.V.P. and V.D.R.; software, M.G., P.B., J.S. and S.S. (Shikha Sharma); validation, E.V.P. and T.M.; formal analysis, E.V.P. and V.D.R.; investigation, A.R., A.C. and T.J.; resources T.M., S.S.M. and S.S. (Svetlana Sushkova); data curation, A.R. and V.D.R.; writing—original draft preparation, A.R., E.V.P., M.G., S.S. (Shikha Sharma) and P.B.; writing—review and editing, A.R., E.V.P., V.D.R. and S.M.Z.; visualization, A.R. and J.S.; supervision, E.V.P. and T.M.; project administration, E.V.P. and T.M.; funding acquisition E.V.P. All authors have read and agreed to the published version of the manuscript.


The research was financially supported by the Ministry of Science and Higher Education of the Russian Federation (no. FENW-2023-0008).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.


The authors acknowledge the support from the Strategic Academic Leadership Program of the Southern Federal University (“Priority 2030”).

Conflicts of Interest

The authors declare no conflict of interest.


BGCBiosynthetic gene cluster
CIDCollision-induced dissociation
CLPCyclic lipopeptide
DNADeoxyribose Nucleic Acid
EPAEnvironmental Protection Agency
ESIElectron spray ionization
ETDElectron transfer dissociation
FAOFood and Agriculture Organization
FDAFood and Drug Administration
HCNHydrogen cyanide
HPLCHigh-performance liquid chromatography
LCLiquid Chromatography
MALDI TOFMatrix-assisted laser desorption/ionization-Time of Flight
MAPKMitogen-Activated Protein Kinase
MICMinimum Inhibitory Concentration
MMPMitochondrial membrane potential
MPAMethylphenyl acetate
MSMass Spectroscopy
NMRNuclear Magnetic Resonance
NRPsNon-Ribosomal Peptides
NRPSNon-Ribosomal Peptide synthetase
PAAPhenylacetic acid
PARPPoly (ADP-ribose) polymerase
PGPBPlant-Growth-Promoting Bacteria
RNARibose Nucleic Acid
ROSReactive Oxygen Species
TLCThin-Layer chromatography
UPLCUltra-high-performance liquid chromatography
VOCVolatile organic compounds


  1. WFP; WHO; UNICEF. The State of Food Security and Nutrition in the World 2022. 2022. Available online: (accessed on 28 May 2023).
  2. Chavas, J.; Rivieccio, G.; Di Falco, S.; De Luca, G.; Capitanio, F. Agricultural Diversification, Productivity, and Food Security across Time and Space. Agric. Econ. 2022, 53, 41–58. [Google Scholar] [CrossRef]
  3. Pixley, K.V.; Falck-Zepeda, J.B.; Paarlberg, R.L.; Phillips, P.W.B.; Slamet-Loedin, I.H.; Dhugga, K.S.; Campos, H.; Gutterson, N. Genome-Edited Crops for Improved Food Security of Smallholder Farmers. Nat. Genet. 2022, 54, 364–367. [Google Scholar] [CrossRef]
  4. FAO 2021. Available online: (accessed on 21 June 2023).
  5. Bernardo-Cravo, A.P.; Schmeller, D.S.; Chatzinotas, A.; Vredenburg, V.T.; Loyau, A. Environmental Factors and Host Microbiomes Shape Host–Pathogen Dynamics. Trends Parasitol. 2020, 36, 616–633. [Google Scholar] [CrossRef]
  6. Von Wintersdorff, C.J.H.; Penders, J.; Van Niekerk, J.M.; Mills, N.D.; Majumder, S.; Van Alphen, L.B.; Savelkoul, P.H.M.; Wolffs, P.F.G. Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer. Front. Microbiol. 2016, 7, 173. [Google Scholar] [CrossRef] [Green Version]
  7. Rodríguez-Beltrán, J.; DelaFuente, J.; Leon-Sampedro, R.; MacLean, R.C.; San Millan, A. Beyond Horizontal Gene Transfer: The Role of Plasmids in Bacterial Evolution. Nat. Rev. Microbiol. 2021, 19, 347–359. [Google Scholar] [CrossRef]
  8. Zeilinger, S.; Gupta, V.K.; Dahms, T.E.S.; Silva, R.N.; Singh, H.B.; Upadhyay, R.S.; Gomes, E.V.; Tsui, C.K.M.; Chandra Nayak, S. Friends or Foes? Emerging Insights from Fungal Interactions with Plants. FEMS Microbiol. Rev. 2016, 40, 182–207. [Google Scholar] [CrossRef] [Green Version]
  9. Brundrett, M.C. Mycorrhizal Associations and Other Means of Nutrition of Vascular Plants: Understanding the Global Diversity of Host Plants by Resolving Conflicting Information and Developing Reliable Means of Diagnosis. Plant. Soil. 2009, 320, 37–77. [Google Scholar] [CrossRef]
  10. Tedersoo, L.; Bahram, M.; Zobel, M. How Mycorrhizal Associations Drive Plant Population and Community Biology. Science 2020, 367, eaba1223. [Google Scholar] [CrossRef]
  11. Ranjan, A.; Chauhan, A.; Rajput, V.D.; Basniwal, R.K.; Minkina, T.; Sushkova, S.; Jindal, T. Genetic Basis of Fungal Endophytic Bioactive Compounds Synthesis, Modulation, and Their Biotechnological Application. In Bacterial Endophytes for Sustainable Agriculture and Environmental Management; Springer: Berlin/Heidelberg, Germany, 2022; pp. 157–186. [Google Scholar]
  12. Doehlemann, G.; Ökmen, B.; Zhu, W.; Sharon, A. Plant Pathogenic Fungi. Microbiol. Spectr. 2017, 5, 1–23. [Google Scholar] [CrossRef]
  13. Lockwood, J.L. Evolution of Concepts Associated with Soilborne Plant Pathogens. Annu. Rev. Phytopathol. 1988, 26, 93–121. [Google Scholar] [CrossRef]
  14. Ranjan, A.; Jindal, T.; Ranjan, A.; Jindal, T. Overview of Organophosphate Compounds. Toxicol. Organophosphate Poisoning New Insights 2022, 1, 1–25. [Google Scholar]
  15. Ranjan, A.; Jindal, T. Toxicology of Organophosphate Poisoning in Human. In Toxicology of Organophosphate Poisoning; Springer: Berlin/Heidelberg, German, 2022; pp. 27–43. [Google Scholar]
  16. Curl, C.L.; Spivak, M.; Phinney, R.; Montrose, L. Synthetic Pesticides and Health in Vulnerable Populations: Agricultural Workers. Curr. Environ. Health Rep. 2020, 7, 13–29. [Google Scholar] [CrossRef]
  17. John, C.J.; Kumar, S.; Ge, M. Probiotic Prospects of PGPR for Green and Sustainable Agriculture. Arch. Phytopathol. Plant Prot. 2020, 53, 899–914. [Google Scholar] [CrossRef]
  18. Dimkić, I.; Janakiev, T.; Petrović, M.; Degrassi, G.; Fira, D. Plant-Associated Bacillus and Pseudomonas Antimicrobial Activities in Plant Disease Suppression via Biological Control Mechanisms—A Review. Physiol. Mol. Plant. Pathol. 2022, 117, 101754. [Google Scholar] [CrossRef]
  19. Migunova, V.D.; Sasanelli, N. Bacteria as Biocontrol Tool against Phytoparasitic Nematodes. Plants 2021, 10, 389. [Google Scholar] [CrossRef]
  20. Wang, H.; Liu, R.; You, M.P.; Barbetti, M.J.; Chen, Y. Pathogen Biocontrol Using Plant Growth-Promoting Bacteria (PGPR): Role of Bacterial Diversity. Microorganisms 2021, 9, 1988. [Google Scholar] [CrossRef]
  21. Vejan, P.; Abdullah, R.; Khadiran, T.; Ismail, S.; Nasrulhaq Boyce, A. Role of Plant Growth Promoting Rhizobacteria in Agricultural Sustainability—A Review. Molecules 2016, 21, 573. [Google Scholar] [CrossRef] [Green Version]
  22. Wani, S.P.; Gopalakrishnan, S. Plant Growth-Promoting Microbes for Sustainable Agriculture. In Plant Growth Promoting Rhizobacteria (PGPR): Prospects for Sustainable Agriculture; Springer: Berlin/Heidelberg, Germany, 2019; pp. 19–45. [Google Scholar]
  23. Dimkic, I.; Stankovic, S.; Nišavic, M.; Petkovic, M.; Ristivojevic, P.; Fira, D.; Beric, T. The Profile and Antimicrobial Activity of Bacillus Lipopeptide Extracts of Five Potential Biocontrol Strains. Front. Microbiol. 2017, 8, 44–55. [Google Scholar] [CrossRef] [Green Version]
  24. Li, Z.; de Vries, R.H.; Chakraborty, P.; Song, C.; Zhao, X.; Scheffers, D.-J.; Roelfes, G.; Kuipers, O.P. Novel Modifications of Nonribosomal Peptides from Brevibacillus laterosporus MG64 and Investigation of Their Mode of Action. Appl. Environ. Microbiol. 2020, 86, e01981-20. [Google Scholar] [CrossRef]
  25. Rajput, D.V.; Minkina, T.; Kumari, A.; Shende, S.S.; Ranjan, A.; Faizan, M.; Barakvov, A.; Gromovik, A.; Gorbunova, N.; Rajput, P. A Review on Nanobioremediation Approaches for Restoration of Contaminated Soil. Eurasian J. Soil Sci. 2022, 11, 43–60. [Google Scholar] [CrossRef]
  26. Gu, Q.; Qiao, J.; Wang, R.; Lu, J.; Wang, Z.; Li, P.; Zhang, L.; Ali, Q.; Khan, A.R.; Gao, X. The Role of Pyoluteorin from Pseudomonas protegens Pf-5 in Suppressing the Growth and Pathogenicity of Pantoea ananatis on Maize. Int. J. Mol. Sci. 2022, 23, 6431. [Google Scholar] [CrossRef]
  27. Hua, G.K.H.; Wang, L.; Chen, J.; Ji, P. Biological Control of Fusarium wilt on Watermelon by Fluorescent Pseudomonads. Biocontrol Sci. Technol. 2020, 30, 212–227. [Google Scholar] [CrossRef]
  28. Wang, X.; Mavrodi, D.V.; Ke, L.; Mavrodi, O.V.; Yang, M.; Thomashow, L.S.; Zheng, N.; Weller, D.M.; Zhang, J. Biocontrol and Plant Growth-promoting Activity of Rhizobacteria from C Hinese Fields with Contaminated Soils. Microb. Biotechnol. 2015, 8, 404–418. [Google Scholar] [CrossRef]
  29. Caulier, S.; Gillis, A.; Colau, G.; Licciardi, F.; Liépin, M.; Desoignies, N.; Modrie, P.; Legrève, A.; Mahillon, J.; Bragard, C. Versatile Antagonistic Activities of Soil-Borne Bacillus spp. and Pseudomonas spp. against Phytophthora infestans and Other Potato Pathogens. Front. Microbiol. 2018, 9, 143. [Google Scholar] [CrossRef]
  30. Olanrewaju, O.S.; Glick, B.R.; Babalola, O.O. Mechanisms of Action of Plant Growth Promoting Bacteria. World J. Microbiol. Biotechnol. 2017, 33, 197. [Google Scholar] [CrossRef] [Green Version]
  31. Hur, G.H.; Vickery, C.R.; Burkart, M.D. Explorations of Catalytic Domains in Non-Ribosomal Peptide Synthetase Enzymology. Nat. Prod. Rep. 2012, 29, 1074–1098. [Google Scholar] [CrossRef] [Green Version]
  32. Fira, D.; Dimkić, I.; Berić, T.; Lozo, J.; Stanković, S. Biological Control of Plant Pathogens by Bacillus Species. J. Biotechnol. 2018, 285, 44–55. [Google Scholar] [CrossRef]
  33. Sivasakthi, S.; Usharani, G.; Saranraj, P. Biocontrol Potentiality of Plant Growth Promoting Bacteria (PGPR)-Pseudomonas fluorescens and Bacillus subtilis: A Review. Afr. J. Agric. Res. 2014, 9, 1265–1277. [Google Scholar]
  34. Niu, X.; Thaochan, N.; Hu, Q. Diversity of Linear Non-Ribosomal Peptide in Biocontrol Fungi. J. Fungi 2020, 6, 61. [Google Scholar] [CrossRef]
  35. Miller, B.R.; Gulick, A.M. Structural Biology of Nonribosomal Peptide Synthetases. Nonribosomal Pept. Polyketide Biosynth. Methods Protos. 2016, 1401, 3–29. [Google Scholar]
  36. Strieker, M.; Tanović, A.; Marahiel, M.A. Nonribosomal Peptide Synthetases: Structures and Dynamics. Curr. Opin. Struct. Biol. 2010, 20, 234–240. [Google Scholar] [CrossRef]
  37. Schwarzer, D.; Finking, R.; Marahiel, M.A. Nonribosomal Peptides: From Genes to Products. Nat. Prod. Rep. 2003, 20, 275–287. [Google Scholar] [CrossRef]
  38. Walsh, C.T.; Chen, H.; Keating, T.A.; Hubbard, B.K.; Losey, H.C.; Luo, L.; Marshall, C.G.; Miller, D.A.; Patel, H.M. Tailoring Enzymes That Modify Nonribosomal Peptides during and after Chain Elongation on NRPS Assembly Lines. Curr. Opin. Chem. Biol. 2001, 5, 525–534. [Google Scholar] [CrossRef]
  39. Wan, C.; Fan, X.; Lou, Z.; Wang, H.; Olatunde, A.; Rengasamy, K.R.R. Iturin: Cyclic Lipopeptide with Multifunction Biological Potential. Crit. Rev. Food Sci. Nutr. 2022, 62, 7976–7988. [Google Scholar] [CrossRef]
  40. Mnif, I.; Ghribi, D. Potential of Bacterial Derived Biopesticides in Pest Management. Crop. Prot. 2015, 77, 52–64. [Google Scholar] [CrossRef]
  41. Delcambe, L.; Peypoux, F.; Besson, F.; Guinand, M.; Michel, G. Structure of Iturin and Iturin-like Substances. Biochem. Soc. Trans. 1977, 5, 1122–1124. [Google Scholar] [CrossRef] [Green Version]
  42. Maldonado Desena, F.; De la Cruz Ceferino, N.; Gómez Cornelio, S.; Alvarez Villagomez, C.; Herrera Candelario, J.L.; De la Rosa García, S. Bacteria Halotolerant from Karst Sinkholes as a Source of Biosurfactants and Bioemulsifiers. Microorganisms 2022, 10, 1264. [Google Scholar] [CrossRef]
  43. Besson, F.; Peypoux, F.; Michel, G.; Delcambe, L. Identification of Antibiotics of Iturin Group in Various Strains of Bacillus subtilis. J. Antibiot. 1978, 31, 284–288. [Google Scholar] [CrossRef] [Green Version]
  44. Stein, T. Bacillus subtilis Antibiotics: Structures, Syntheses and Specific Functions. Mol. Microbiol. 2005, 56, 845–857. [Google Scholar] [CrossRef]
  45. Ongena, M.; Jacques, P. Bacillus Lipopeptides: Versatile Weapons for Plant Disease Biocontrol. Trends Microbiol. 2008, 16, 115–125. [Google Scholar] [CrossRef]
  46. Thimon, L.; Peypoux, F.; Dana Maget, R.; Roux, B.; Michel, G. Interactions of Bioactive Lipopeptides, Iturin A and Surfactin from Bacillus subtilis. Biotechnol. Appl. Biochem. 1992, 16, 144–151. [Google Scholar]
  47. Tsuge, K.; Akiyama, T.; Shoda, M. Cloning, Sequencing, and Characterization of the Iturin A Operon. J. Bacteriol. 2001, 183, 6265–6273. [Google Scholar] [CrossRef] [Green Version]
  48. Das, P.; Mukherjee, S.; Sen, R. Genetic Regulations of the Biosynthesis of Microbial Surfactants: An Overview. Biotechnol. Genet. Eng. Rev. 2008, 25, 165–186. [Google Scholar] [CrossRef]
  49. Singh, D.; Yadav, D.K.; Sinha, S.; Mondal, K.K.; Singh, G.; Pandey, R.R.; Singh, R. Genetic Diversity of Iturin Producing Strains of Bacillus Species Antagonistic to Ralstonia solanacerarum Causing Bacterial Wilt Disease in Tomato. Afr. J. Microbiol. Res. 2013, 7, 5459–5470. [Google Scholar]
  50. Rasiya, K.T.; Sebastian, D. Iturin and Surfactin from the Endophyte Bacillus amyloliquefaciens Strain RKEA3 Exhibits Antagonism against Staphylococcus aureus. Biocatal. Agric. Biotechnol. 2021, 36, 102125. [Google Scholar]
  51. Ntushelo, K.; Ledwaba, L.K.; Rauwane, M.E.; Adebo, O.A.; Njobeh, P.B. The Mode of Action of Bacillus Species against Fusarium graminearum, Tools for Investigation, and Future Prospects. Toxins 2019, 11, 606. [Google Scholar] [CrossRef] [Green Version]
  52. Balleza, D.; Alessandrini, A.; Beltrán García, M.J. Role of Lipid Composition, Physicochemical Interactions, and Membrane Mechanics in the Molecular Actions of Microbial Cyclic Lipopeptides. J. Membr. Biol. 2019, 252, 131–157. [Google Scholar] [CrossRef]
  53. Ferrarini, E.; De Roo, V.; Geudens, N.; Martins, J.C.; Höfte, M. Altering in Vivo Membrane Sterol Composition Affects the Activity of the Cyclic Lipopeptides Tolaasin and Sessilin against Pythium. Biochim. Biophys. Acta (BBA)-Biomembr. 2022, 1864, 184008. [Google Scholar] [CrossRef]
  54. Gong, A.-D.; Li, H.-P.; Yuan, Q.-S.; Song, X.-S.; Yao, W.; He, W.-J.; Zhang, J.-B.; Liao, Y.-C. Antagonistic Mechanism of Iturin A and Plipastatin A from Bacillus amyloliquefaciens S76-3 from Wheat Spikes against Fusarium graminearum. PLoS ONE 2015, 10, e0116871. [Google Scholar] [CrossRef] [Green Version]
  55. Wang, Y.; Zhang, C.; Liang, J.; Wu, L.; Gao, W.; Jiang, J. Iturin A Extracted from Bacillus subtilis WL-2 Affects Phytophthora infestans via Cell Structure Disruption, Oxidative Stress, and Energy Supply Dysfunction. Front. Microbiol. 2020, 11, 536083. [Google Scholar] [CrossRef]
  56. Jacques, P. Surfactin and Other Lipopeptides from Bacillus spp. Biosurfactants Genes Appl. 2011, 57–91. [Google Scholar]
  57. Kakinuma, A.; Sugino, H.; Isono, M.; Tamura, G.; Arima, K. Determination of Fatty Acid in Surfactin and Elucidation of the Total Structure of Surfactin. Agric. Biol. Chem. 1969, 33, 973–976. [Google Scholar] [CrossRef]
  58. Chen, X.; Lu, Y.; Shan, M.; Zhao, H.; Lu, Z.; Lu, Y. A Mini-Review: Mechanism of Antimicrobial Action and Application of Surfactin. World J. Microbiol. Biotechnol. 2022, 38, 143. [Google Scholar] [CrossRef]
  59. Abbasi Moud, A. Rheology and Microscopy Analysis of Polymer–Surfactant Complexes. Colloid. Polym. Sci. 2022, 300, 733–762. [Google Scholar] [CrossRef]
  60. Sharma, D.; Singh, S.S.; Baindara, P.; Sharma, S.; Khatri, N.; Grover, V.; Patil, P.B.; Korpole, S. Surfactin like Broad Spectrum Antimicrobial Lipopeptide Co-Produced with Sublancin from Bacillus subtilis Strain A52: Dual Reservoir of Bioactives. Front. Microbiol. 2020, 11, 1167. [Google Scholar] [CrossRef]
  61. Abdel-Mawgoud, A.M.; Aboulwafa, M.M.; Hassouna, N.A.-H. Characterization of Surfactin Produced by Bacillus subtilis Isolate BS5. Appl. Biochem. Biotechnol. 2008, 150, 289–303. [Google Scholar] [CrossRef]
  62. Liu, L.; Jin, X.; Lu, X.; Guo, L.; Lu, P.; Yu, H.; Lv, B. Mechanisms of Surfactin from Bacillus subtilis SF1 against Fusarium foetens: A Novel Pathogen Inducing Potato Wilt. J. Fungi 2023, 9, 367. [Google Scholar] [CrossRef]
  63. Tang, Q.; Bie, X.; Lu, Z.; Lv, F.; Tao, Y.; Qu, X. Effects of Fengycin from Bacillus subtilis FmbJ on Apoptosis and Necrosis in Rhizopus stolonifer. J. Microbiol. 2014, 52, 675–680. [Google Scholar] [CrossRef]
  64. Yang, H.; Li, X.; Li, X.; Yu, H.; Shen, Z. Identification of Lipopeptide Isoforms by MALDI-TOF-MS/MS Based on the Simultaneous Purification of Iturin, Fengycin, and Surfactin by RP-HPLC. Anal. Bioanal. Chem. 2015, 407, 2529–2542. [Google Scholar] [CrossRef]
  65. Wu, C.-Y.; Chen, C.-L.; Lee, Y.-H.; Cheng, Y.-C.; Wu, Y.-C.; Shu, H.-Y.; Goötz, F.; Liu, S.-T. Nonribosomal Synthesis of Fengycin on an Enzyme Complex Formed by Fengycin Synthetases. J. Biol. Chem. 2007, 282, 5608–5616. [Google Scholar] [CrossRef] [Green Version]
  66. Medeot, D.B.; Fernandez, M.; Morales, G.M.; Jofré, E. Fengycins from Bacillus amyloliquefaciens MEP218 Exhibit Antibacterial Activity by Producing Alterations on the Cell Surface of the Pathogens Xanthomonas axonopodis pv. vesicatoria and Pseudomonas aeruginosa PA01. Front. Microbiol. 2020, 10, 3107. [Google Scholar] [CrossRef] [Green Version]
  67. Wei, Y.-H.; Wang, L.-C.; Chen, W.-C.; Chen, S.-Y. Production and Characterization of Fengycin by Indigenous Bacillus subtilis F29-3 Originating from a Potato Farm. Int. J. Mol. Sci. 2010, 11, 4526–4538. [Google Scholar] [CrossRef] [Green Version]
  68. Karthika, S.; Midhun, S.J.; Jisha, M.S. A Potential Antifungal and Growth-Promoting Bacterium bacillus sp. KTMA4 from Tomato Rhizosphere. Microb. Pathog. 2020, 142, 104049. [Google Scholar] [CrossRef]
  69. Abd El-Daim, I.A.; Bejai, S.; Fridborg, I.; Meijer, J. Identifying Potential Molecular Factors Involved in Bacillus amyloliquefaciens 5113 Mediated Abiotic Stress Tolerance in Wheat. Plant. Biol. 2018, 20, 271–279. [Google Scholar] [CrossRef]
  70. Seifi Kalhor, M.; Aliniaeifard, S.; Seif, M.; Javadi, E.; Bernard, F.; Li, T.; Lastochkina, O. Rhizobacterium Bacillus subtilis Reduces Toxic Effects of High Electrical Conductivity in Soilless Culture of Lettuce. In Proceedings of the International Symposium on New Technologies for Environment Control, Energy-Saving and Crop Production in Greenhouse and Plant 1227, Beijing, China, 20–24 August 2017; pp. 471–478. [Google Scholar]
  71. Romero, D.; De Vicente, A.; Rakotoaly, R.H.; Dufour, S.E.; Veening, J.-W.; Arrebola, E.; Cazorla, F.M.; Kuipers, O.P.; Paquot, M.; Pérez-García, A. The Iturin and Fengycin Families of Lipopeptides Are Key Factors in Antagonism of Bacillus subtilis toward Podosphaera fusca. Mol. Plant-Microbe Interact. 2007, 20, 430–440. [Google Scholar] [CrossRef] [Green Version]
  72. Zhang, L.; Sun, C. Fengycins, Cyclic Lipopeptides from Marine Bacillus subtilis Strains, Kill the Plant-Pathogenic Fungus Magnaporthe Grisea by Inducing Reactive Oxygen Species Production and Chromatin Condensation. Appl. Environ. Microbiol. 2018, 84, e00445-18. [Google Scholar] [CrossRef] [Green Version]
  73. Haddoudi, I.; Cabrefiga, J.; Mora, I.; Mhadhbi, H.; Montesinos, E.; Mrabet, M. Biological Control of Fusarium wilt Caused by Fusarium equiseti in Vicia faba with Broad Spectrum Antifungal Plant-Associated Bacillus spp. Biol. Control 2021, 160, 104671. [Google Scholar] [CrossRef]
  74. Nerling, D.; Castoldi, C.T.; Ehrhardt-Brocardo, N.C.M. The Role of PGPR-Polar Metabolites, Metal-Chelator Compounds and Antibiotics on Plant Growth. Second. Metab. Volatiles PGPR Plant-Growth Promot. 2022, 7, 77–93. [Google Scholar]
  75. Siddiqui, Z.A. PGPR: Prospective Biocontrol Agents of Plant Pathogens. In PGPR: Biocontrol and Biofertilization; Springer: Berlin/Heidelberg, Germany, 2005; pp. 111–142. [Google Scholar]
  76. Gimenez, D.; Phelan, A.; Murphy, C.D.; Cobb, S.L. Fengycin A Analogues with Enhanced Chemical Stability and Antifungal Properties. Org. Lett. 2021, 23, 4672–4676. [Google Scholar] [CrossRef]
  77. Wang, H.; Fewer, D.P.; Holm, L.; Rouhiainen, L.; Sivonen, K. Atlas of Nonribosomal Peptide and Polyketide Biosynthetic Pathways Reveals Common Occurrence of Nonmodular Enzymes. Proc. Natl. Acad. Sci. USA 2014, 111, 9259–9264. [Google Scholar] [CrossRef] [Green Version]
  78. Agrawal, S.; Acharya, D.; Adholeya, A.; Barrow, C.J.; Deshmukh, S.K. Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer Potential. Front. Pharmacol. 2017, 8, 828. [Google Scholar] [CrossRef]
  79. Weissman, K.J. The Structural Biology of Biosynthetic Megaenzymes. Nat. Chem. Biol. 2015, 11, 660–670. [Google Scholar] [CrossRef]
  80. Kittilä, T.; Kittel, C.; Tailhades, J.; Butz, D.; Schoppet, M.; Büttner, A.; Goode, R.J.A.; Schittenhelm, R.B.; van Pee, K.-H.; Süssmuth, R.D. Halogenation of Glycopeptide Antibiotics Occurs at the Amino Acid Level during Non-Ribosomal Peptide Synthesis. Chem. Sci. 2017, 8, 5992–6004. [Google Scholar] [CrossRef] [Green Version]
  81. Abderrahmani, A.; Tapi, A.; Nateche, F.; Chollet, M.; Leclère, V.; Wathelet, B.; Hacene, H.; Jacques, P. Bioinformatics and Molecular Approaches to Detect NRPS Genes Involved in the Biosynthesis of Kurstakin from Bacillus thuringiensis. Appl. Microbiol. Biotechnol. 2011, 92, 571–581. [Google Scholar] [CrossRef]
  82. Martínez-Núñez, M.A. Nonribosomal Peptides Synthetases and Their Applications in Industry. Sustain. Chem. Process. 2016, 4, 13. [Google Scholar] [CrossRef] [Green Version]
  83. Bloudoff, K.; Schmeing, T.M. Structural and Functional Aspects of the Nonribosomal Peptide Synthetase Condensation Domain Superfamily: Discovery, Dissection and Diversity. Biochim. Biophys. Acta (BBA)-Proteins Proteom. 2017, 1865, 1587–1604. [Google Scholar] [CrossRef]
  84. Luo, C.; Liu, X.; Zhou, X.; Guo, J.; Truong, J.; Wang, X.; Zhou, H.; Li, X.; Chen, Z. Unusual Biosynthesis and Structure of Locillomycins from Bacillus subtilis 916. Appl. Environ. Microbiol. 2015, 81, 6601–6609. [Google Scholar] [CrossRef] [Green Version]
  85. Cai, X.; Zhao, L.; Bode, H.B. Engineering of Specific Single-Module Nonribosomal Peptide Synthetases of the RXP Type for the Production of Defined Peptides. ACS Synth. Biol. 2022, 12, 203–212. [Google Scholar] [CrossRef]
  86. Oide, S.; Turgeon, B.G. Natural Roles of Nonribosomal Peptide Metabolites in Fungi. Mycoscience 2020, 61, 101–110. [Google Scholar] [CrossRef]
  87. Mengin-Lecreulx, D.; Allen, N.E.; Hobbs, J.N.; van Heijenoort, J. Inhibition of Peptidoglycan Biosynthesis in Bacillus Megaterium by Daptomycin. FEMS Microbiol. Lett. 1990, 69, 245–248. [Google Scholar] [CrossRef]
  88. Wang, F.; Zhou, H.; Olademehin, O.P.; Kim, S.J.; Tao, P. Insights into Key Interactions between Vancomycin and Bacterial Cell Wall Structures. ACS Omega 2018, 3, 37–45. [Google Scholar] [CrossRef]
  89. Liu, J.; Volk, K.J.; Lee, M.S.; Pucci, M.; Handwerger, S. Binding Studies of Vancomycin to the Cytoplasmic Peptidoglycan Precursors by Affinity Capillary Electrophoresis. Anal. Chem. 1994, 66, 2412–2416. [Google Scholar] [CrossRef]
  90. Seydlová, G.; Sokol, A.; Lišková, P.; Konopásek, I.; Fišer, R. Daptomycin Pore Formation and Stoichiometry Depend on Membrane Potential of Target Membrane. Antimicrob. Agents Chemother. 2019, 63, e01589-18. [Google Scholar] [CrossRef] [Green Version]
  91. Siewert, G.; Strominger, J.L. Bacitracin: An Inhibitor of the Dephosphorylation of Lipid Pyrophosphate, an Intermediate in the Biosynthesis of the Peptidoglycan of Bacterial Cell Walls. Proc. Natl. Acad. Sci. USA 1967, 57, 767–773. [Google Scholar] [CrossRef] [Green Version]
  92. Economou, N.J.; Cocklin, S.; Loll, P.J. High-Resolution Crystal Structure Reveals Molecular Details of Target Recognition by Bacitracin. Proc. Natl. Acad. Sci. USA 2013, 110, 14207–14212. [Google Scholar] [CrossRef] [Green Version]
  93. Liu, Y.; Lu, J.; Sun, J.; Zhu, X.; Zhou, L.; Lu, Z.; Lu, Y. C16-Fengycin A Affect the Growth of Candida albicans by Destroying Its Cell Wall and Accumulating Reactive Oxygen Species. Appl. Microbiol. Biotechnol. 2019, 103, 8963–8975. [Google Scholar] [CrossRef]
  94. Zakharova, A.A.; Efimova, S.S.; Ostroumova, O.S. Lipid Microenvironment Modulates the Pore-Forming Ability of Polymyxin B. Antibiotics 2022, 11, 1445. [Google Scholar] [CrossRef]
  95. Zhang, H.; Srinivas, S.; Xu, Y.; Wei, W.; Feng, Y. Genetic and Biochemical Mechanisms for Bacterial Lipid A Modifiers Associated with Polymyxin Resistance. Trends Biochem. Sci. 2019, 44, 973–988. [Google Scholar] [CrossRef]
  96. Gray, D.A.; Wenzel, M. More than a Pore: A Current Perspective on the in Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin. Antibiotics 2020, 9, 17. [Google Scholar] [CrossRef] [Green Version]
  97. Killian, J.A. Gramicidin and Gramicidin-Lipid Interactions. Biochim. Biophys. Acta (BBA)-Rev. Biomembr. 1992, 1113, 391–425. [Google Scholar] [CrossRef]
  98. Fang, S.-T.; Huang, S.-H.; Yang, C.-H.; Liou, J.-W.; Mani, H.; Chen, Y.-C. Effects of Calcium Ions on the Antimicrobial Activity of Gramicidin A. Biomolecules 2022, 12, 1799. [Google Scholar] [CrossRef]
  99. Qian, S.; Lu, H.; Sun, J.; Zhang, C.; Zhao, H.; Lu, F.; Bie, X.; Lu, Z. Antifungal Activity Mode of Aspergillus ochraceus by Bacillomycin D and Its Inhibition of Ochratoxin A (OTA) Production in Food Samples. Food Control. 2016, 60, 281–288. [Google Scholar] [CrossRef]
  100. Nain, Z.; Mansur, F.J.; Syed, S.B.; Islam, M.A.; Azakami, H.; Islam, M.R.; Karim, M.M. Inhibition of Biofilm Formation, Quorum Sensing and Other Virulence Factors in Pseudomonas aeruginosa by Polyphenols of Gynura procumbens Leaves. J. Biomol. Struct. Dyn. 2022, 40, 5357–5371. [Google Scholar] [CrossRef]
  101. Stincone, P.; Fonseca Veras, F.; Micalizzi, G.; Donnarumma, D.; Vitale Celano, G.; Petras, D.; de Angelis, M.; Mondello, L.; Brandelli, A. Listeria Monocytogenes Exposed to Antimicrobial Peptides Displays Differential Regulation of Lipids and Proteins Associated to Stress Response. Cell. Mol. Life Sci. 2022, 79, 263. [Google Scholar] [CrossRef]
  102. Silva-Stenico, M.E.; Silva, C.S.P.; Lorenzi, A.S.; Shishido, T.K.; Etchegaray, A.; Lira, S.P.; Moraes, L.A.B.; Fiore, M.F. Non-Ribosomal Peptides Produced by Brazilian Cyanobacterial Isolates with Antimicrobial Activity. Microbiol. Res. 2011, 166, 161–175. [Google Scholar] [CrossRef]
  103. Kaniusaite, M.; Goode, R.J.A.; Tailhades, J.; Schittenhelm, R.B.; Cryle, M.J. Exploring Modular Reengineering Strategies to Redesign the Teicoplanin Non-Ribosomal Peptide Synthetase. Chem. Sci. 2020, 11, 9443–9458. [Google Scholar] [CrossRef]
  104. Wollinsky, B.; Li, S.-M. Detection and Purification of Non-Ribosomal Peptide Synthetase Products in Neosartorya fischeri. Fungal Second. Metab. Methods Protoc. 2012, 944, 111–119. [Google Scholar]
  105. Behsaz, B.; Bode, E.; Gurevich, A.; Shi, Y.-N.; Grundmann, F.; Acharya, D.; Caraballo-Rodríguez, A.M.; Bouslimani, A.; Panitchpakdi, M.; Linck, A. Integrating Genomics and Metabolomics for Scalable Non-Ribosomal Peptide Discovery. Nat. Commun. 2021, 12, 3225. [Google Scholar] [CrossRef]
  106. Novák, J.; Lemr, K.; Schug, K.A.; Havlíček, V. CycloBranch: De Novo Sequencing of Nonribosomal Peptides from Accurate Product Ion Mass Spectra. J. Am. Soc. Mass. Spectrom. 2015, 26, 1780–1786. [Google Scholar] [CrossRef] [Green Version]
  107. Sarnowski, C.P.; Bikaki, M.; Leitner, A. Cross-Linking and Mass Spectrometry as a Tool for Studying the Structural Biology of Ribonucleoproteins. Structure 2022, 30, 441–461. [Google Scholar] [CrossRef]
  108. Munakata, Y.; Heuson, E.; Daboudet, T.; Deracinois, B.; Duban, M.; Hehn, A.; Coutte, F.; Slezack-Deschaumes, S. Screening of Antimicrobial Activities and Lipopeptide Production of Endophytic Bacteria Isolated from Vetiver Roots. Microorganisms 2022, 10, 209. [Google Scholar] [CrossRef]
  109. Fortinez, C.M.; Bloudoff, K.; Harrigan, C.; Sharon, I.; Strauss, M.; Schmeing, T.M. Structures and Function of a Tailoring Oxidase in Complex with a Nonribosomal Peptide Synthetase Module. Nat. Commun. 2022, 13, 548. [Google Scholar] [CrossRef]
  110. Castro, G.S.; Sousa, T.F.; da Silva, G.F.; Pedroso, R.C.N.; Menezes, K.S.; Soares, M.A.; Dias, G.M.; Santos, A.O.; Yamagishi, M.E.B.; Faria, J.V. Characterization of Peptaibols Produced by a Marine Strain of the Fungus Trichoderma endophyticum via Mass Spectrometry, Genome Mining and Phylogeny-Based Prediction. Metabolites 2023, 13, 221. [Google Scholar] [CrossRef]
  111. Kersten, R.D.; Yang, Y.-L.; Xu, Y.; Cimermancic, P.; Nam, S.-J.; Fenical, W.; Fischbach, M.A.; Moore, B.S.; Dorrestein, P.C. A Mass Spectrometry–Guided Genome Mining Approach for Natural Product Peptidogenomics. Nat. Chem. Biol. 2011, 7, 794–802. [Google Scholar] [CrossRef] [Green Version]
  112. Dorrestein, P.C.; Kelleher, N.L. Dissecting Non-Ribosomal and Polyketide Biosynthetic Machineries Using Electrospray Ionization Fourier-Transform Mass Spectrometry. Nat. Prod. Rep. 2006, 23, 893–918. [Google Scholar] [CrossRef]
  113. Wills, R.H.; O’connor, P.B. Structural Characterization of Actinomycin D Using Multiple Ion Isolation and Electron Induced Dissociation. J. Am. Soc. Mass. Spectrom. 2013, 25, 186–195. [Google Scholar] [CrossRef]
  114. Molinski, T.F. Microscale Methodology for Structure Elucidation of Natural Products. Curr. Opin. Biotechnol. 2010, 21, 819–826. [Google Scholar] [CrossRef] [Green Version]
  115. Mohimani, H.; Liu, W.-T.; Kersten, R.D.; Moore, B.S.; Dorrestein, P.C.; Pevzner, P.A. NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery. J. Nat. Prod. 2014, 77, 1902–1909. [Google Scholar] [CrossRef] [Green Version]
  116. Götze, S.; Vij, R.; Burow, K.; Thome, N.; Urbat, L.; Schlosser, N.; Pflanze, S.; Müller, R.; Hänsch, V.G.; Schlabach, K. Ecological Niche-Inspired Genome Mining Leads to the Discovery of Crop-Protecting Nonribosomal Lipopeptides Featuring a Transient Amino Acid Building Block. J. Am. Chem. Soc. 2023, 145, 2342–2353. [Google Scholar] [CrossRef]
  117. Reimer, J.M.; Eivaskhani, M.; Harb, I.; Guarné, A.; Weigt, M.; Schmeing, T.M. Structures of a Dimodular Nonribosomal Peptide Synthetase Reveal Conformational Flexibility. Science 2019, 366, eaaw4388. [Google Scholar] [CrossRef]
  118. Tarry, M.J.; Haque, A.S.; Bui, K.H.; Schmeing, T.M. X-Ray Crystallography and Electron Microscopy of Cross-and Multi-Module Nonribosomal Peptide Synthetase Proteins Reveal a Flexible Architecture. Structure 2017, 25, 783–793. [Google Scholar] [CrossRef]
  119. Corpuz, J.C.; Sanlley, J.O.; Burkart, M.D. Protein-Protein Interface Analysis of the Non-Ribosomal Peptide Synthetase Peptidyl Carrier Protein and Enzymatic Domains. Synth. Syst. Biotechnol. 2022, 7, 677–688. [Google Scholar] [CrossRef]
  120. Kresna, I.D.M.; Wuisan, Z.G.; Pohl, J.-M.; Mettal, U.; Otoya, V.L.; Gand, M.; Marner, M.; Otoya, L.L.; Boöhringer, N.; Vilcinskas, A. Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete. J. Nat. Prod. 2022, 85, 888–898. [Google Scholar] [CrossRef]
  121. Boddy, C.N. Bioinformatics Tools for Genome Mining of Polyketide and Non-Ribosomal Peptides. J. Ind. Microbiol. Biotechnol. 2014, 41, 443–450. [Google Scholar] [CrossRef]
  122. Martínez-Núñez, M.A.; Rodríguez-Escamilla, Z.; y López, V.L. New Strategies to Discover Non-Ribosomal Peptides as a Source of Antibiotics Molecules. In Pharmaceutical Biocatalysis; Jenny Stanford Publishing: Dubai, United Arab Emirates, 2019; pp. 701–720. ISBN 0429353111. [Google Scholar]
  123. Wu, G.; Liu, Y.; Xu, Y.; Zhang, G.; Shen, Q.; Zhang, R. Exploring Elicitors of the Beneficial Rhizobacterium Bacillus amyloliquefaciens SQR9 to Induce Plant Systemic Resistance and Their Interactions with Plant Signaling Pathways. Mol. Plant-Microbe Interact. 2018, 31, 560–567. [Google Scholar] [CrossRef] [Green Version]
  124. Borriss, R.; Wu, H.; Gao, X. Secondary Metabolites of the Plant Growth Promoting Model Rhizobacterium Bacillus velezensis FZB42 Are Involved in Direct Suppression of Plant Pathogens and in Stimulation of Plant-Induced Systemic Resistance. Second. Metab. Plant Growth Promot. Rhizomicroorg. Discov. Appl. 2019, 147–168. [Google Scholar]
  125. Zhou, G.; Qiu, X.; Wu, X.; Lu, S. Horizontal Gene Transfer Is a Key Determinant of Antibiotic Resistance Genes Profiles during Chicken Manure Composting with the Addition of Biochar and Zeolite. J. Hazard. Mater. 2021, 408, 124883. [Google Scholar] [CrossRef]
  126. Liu, Y.; Ding, S.; Shen, J.; Zhu, K. Nonribosomal Antibacterial Peptides That Target Multidrug-Resistant Bacteria. Nat. Prod. Rep. 2019, 36, 573–592. [Google Scholar] [CrossRef] [Green Version]
  127. Sharma, V.; Salwan, R. Antimicrobial Peptides from Biocontrol Agents: Future Wave in Plant Disease Management. In Plant Pathogens; Apple Academic Press: Palm Bay, FL, USA, 2020; pp. 241–267. ISBN 0429057210. [Google Scholar]
  128. Esmaeel, Q.; Pupin, M.; Jacques, P.; Leclère, V. Nonribosomal Peptides and Polyketides of Burkholderia: New Compounds Potentially Implicated in Biocontrol and Pharmaceuticals. Environ. Sci. Pollut. Res. 2018, 25, 29794–29807. [Google Scholar] [CrossRef]
  129. Ishikawa, F.; Ohnishi, R.; Uchida, C.; Tanabe, G. Activity-Based Protein Profiling of a Surfactin-Producing Nonribosomal Peptide Synthetase in Bacillus subtilis. STAR Protoc. 2022, 3, 101462. [Google Scholar] [CrossRef]
  130. Dutta, S.; Yu, S.M.; Lee, Y.H. Assessment of the Contribution of Antagonistic Secondary Metabolites to the Antifungal and Biocontrol Activities of Pseudomonas fluorescens Nbc275. Plant. Pathol. J. 2020, 36, 491–496. [Google Scholar] [CrossRef]
  131. Jähne, J.; Le Thi, T.T.; Blumenscheit, C.; Schneider, A.; Pham, T.L.; Le Thi, P.T.; Blom, J.; Vater, J.; Schweder, T.; Lasch, P. Novel Plant-Associated Brevibacillus and Lysinibacillus Genomospecies Harbor a Rich Biosynthetic Potential of Antimicrobial Compounds. Microorganisms 2023, 11, 168. [Google Scholar] [CrossRef]
  132. Tian, Y.; Ji, S.; Zhang, E.; Chen, Y.; Xu, G.; Chen, X.; Fan, J.; Tang, X. Complete Genome Analysis of Bacillus subtilis TY-1 Reveals Its Biocontrol Potential against Tobacco Bacterial Wilt. Mar. Genom. 2023, 68, 101018. [Google Scholar] [CrossRef]
  133. Clough, S.E.; Jousset, A.; Elphinstone, J.G.; Friman, V. Combining in Vitro and in Vivo Screening to Identify Efficient Pseudomonas Biocontrol Strains against the Phytopathogenic Bacterium Ralstonia solanacearum. Microbiologyopen 2022, 11, e1283. [Google Scholar] [CrossRef]
  134. Deng, X.; Zhang, N.; Li, Y.; Zhu, C.; Qu, B.; Liu, H.; Li, R.; Bai, Y.; Shen, Q.; Falcao Salles, J. Bio-organic Soil Amendment Promotes the Suppression of Ralstonia solanacearum by Inducing Changes in the Functionality and Composition of Rhizosphere Bacterial Communities. New Phytol. 2022, 235, 1558–1574. [Google Scholar] [CrossRef]
  135. Qi, P.; Sun, D.; Wu, T.; Li, Y. Stress Proteins, Nonribosomal Peptide Synthetases, and Polyketide Synthases Regulate Carbon Sources-Mediated Bio-Demulsifying Mechanisms of Nitrate-Reducing Bacterium Gordonia sp. TD-4. J. Hazard. Mater. 2022, 422, 126900. [Google Scholar] [CrossRef]
  136. Zhou, L.; Song, C.; Li, Z.; Kuipers, O.P. Antimicrobial Activity Screening of Rhizosphere Soil Bacteria from Tomato and Genome-Based Analysis of Their Antimicrobial Biosynthetic Potential. BMC Genom. 2021, 22, 29. [Google Scholar] [CrossRef]
  137. Gu, Y.; Wang, J.; Xia, Z.; Wei, H.-L. Characterization of a Versatile Plant Growth-Promoting Rhizobacterium Pseudomonas mediterranea Strain S58. Microorganisms 2020, 8, 334. [Google Scholar] [CrossRef] [Green Version]
  138. Chen, D.M.; Yang, H.J.; Huang, J.G.; Yuan, L. Lysobacter enzymogenes LE16 Autolysates Have Potential as Biocontrol Agents—Lysobacter sp. Autolysates as Biofungicide. J. Appl. Microbiol. 2020, 129, 1684–1692. [Google Scholar] [CrossRef]
  139. Abdelli, F.; Jardak, M.; Elloumi, J.; Stien, D.; Cherif, S.; Mnif, S.; Aifa, S. Antibacterial, Anti-Adherent and Cytotoxic Activities of Surfactin (s) from a Lipolytic Strain Bacillus safensis F4. Biodegradation 2019, 30, 287–300. [Google Scholar] [CrossRef]
  140. Pusztahelyi, T.; Holb, I.J.; Pócsi, I. Secondary Metabolites in Fungus-Plant Interactions. Front. Plant. Sci. 2015, 6, 573. [Google Scholar] [CrossRef] [Green Version]
  141. Tyśkiewicz, R.; Nowak, A.; Ozimek, E.; Jaroszuk-ściseł, J. Trichoderma: The Current Status of Its Application in Agriculture for the Biocontrol of Fungal Phytopathogens and Stimulation of Plant Growth. Int. J. Mol. Sci. 2022, 23, 29. [Google Scholar] [CrossRef]
  142. Daoubi, M.; Pinedo-Rivilla, C.; Rubio, M.B.; Hermosa, R.; Monte, E.; Aleu, J.; Collado, I.G. Hemisynthesis and Absolute Configuration of Novel 6-Pentyl-2H-Pyran-2-One Derivatives from Trichoderma spp. Tetrahedron 2009, 65, 4834–4840. [Google Scholar] [CrossRef] [Green Version]
  143. Vizcaino, J.A.; Sanz, L.; Cardoza, R.E.; Monte, E.; Gutierrez, S. Detection of Putative Peptide Synthetase Genes in Trichoderma Species: Application of This Method to the Cloning of a Gene from T. Harzianum CECT 2413. FEMS Microbiol. Lett. 2005, 244, 139–148. [Google Scholar] [CrossRef] [Green Version]
  144. Zhao, Y.; Selvaraj, J.N.; Xing, F.; Zhou, L.; Wang, Y.; Song, H.; Tan, X.; Sun, L.; Sangare, L.; Folly, Y.M.E.; et al. Antagonistic Action of Bacillus subtilis Strain SG6 on Fusarium graminearum. PLoS ONE 2014, 9, e92486. [Google Scholar] [CrossRef]
  145. Jiang, J.; Gao, L.; Bie, X.; Lu, Z.; Liu, H.; Zhang, C.; Lu, F.; Zhao, H. Identification of Novel Surfactin Derivatives from NRPS Modification of Bacillus subtilis and Its Antifungal Activity against Fusarium moniliforme. BMC Microbiol. 2016, 16, 31. [Google Scholar] [CrossRef] [Green Version]
  146. Sarwar, A.; Hassan, M.N.; Imran, M.; Iqbal, M.; Majeed, S.; Brader, G.; Sessitsch, A.; Hafeez, F.Y. Biocontrol Activity of Surfactin A Purified from Bacillus NH-100 and NH-217 against Rice Bakanae Disease. Microbiol. Res. 2018, 209, 1–13. [Google Scholar] [CrossRef]
  147. Leclère, V.; Béchet, M.; Adam, A.; Guez, J.-S.; Wathelet, B.; Ongena, M.; Thonart, P.; Gancel, F.; Chollet-Imbert, M.; Jacques, P. Mycosubtilin Overproduction by Bacillus subtilis BBG100 Enhances the Organism’s Antagonistic and Biocontrol Activities. Appl. Environ. Microbiol. 2005, 71, 4577–4584. [Google Scholar] [CrossRef] [Green Version]
  148. Niemhom, N.; Kittiwongwattana, C. Biocontrol Potential, Genome and Nonribosomal Peptide Synthetase Gene Expression of Bacillus velezensis 2211. Curr. Appl. Sci. Technol. 2023, 10, 1–17. [Google Scholar] [CrossRef]
  149. Kaur, C.; Fidenza, M.; Ervin, E.; Bais, H.P. SpoA-Dependent Antifungal Activity of a Plant Growth Promoting Rhizobacteria Bacillus subtilis Strain UD1022 against the Dollar Spot Pathogen (Clarireedia jacksonii). Available online: (accessed on 28 May 2023).
  150. Rosier, A.; Pomerleau, M.; Beauregard, P.B.; Samac, D.A.; Bais, H.P. Surfactin and Spo0A-Dependent Antagonism by Bacillus subtilis Strain UD1022 against Medicago sativa Phytopathogens. Plants 2023, 12, 1007. [Google Scholar] [CrossRef]
  151. Doty, S.L.; Joubert, P.M.; Firrincieli, A.; Sher, A.W.; Tournay, R.; Kill, C.; Parikh, S.S.; Okubara, P. Potential Biocontrol Activities of Populus Endophytes against Several Plant Pathogens Using Different Inhibitory Mechanisms. Pathogens 2023, 12, 13. [Google Scholar] [CrossRef]
  152. Songwattana, P.; Boonchuen, P.; Piromyou, P.; Wongdee, J.; Greetatorn, T.; Inthaisong, S.; Tantasawat, P.A.; Teamtisong, K.; Tittabutr, P.; Boonkerd, N. Insights into Antifungal Mechanisms of Bacillus velezensis S141 against Cercospora Leaf Spot in Mungbean (V. radiata). Microbes Environ. 2023, 38, ME22079. [Google Scholar] [CrossRef]
  153. Khatri, S.; Sazinas, P.; Strube, M.L.; Ding, L.; Dubey, S.; Shivay, Y.S.; Sharma, S.; Jelsbak, L. Pseudomonas Is a Key Player in Conferring Disease Suppressiveness in Organic Farming. Plant Soil 2023, 1–20. [Google Scholar] [CrossRef]
  154. Qiao, J.; Zhang, R.; Liu, Y.; Liu, Y. Evaluation of the Biocontrol Efficiency of Bacillus subtilis Wettable Powder on Pepper Root Rot Caused by Fusarium solani. Pathogens 2023, 12, 225. [Google Scholar] [CrossRef]
  155. Yabaneri, C.; Sevim, A. Endophytic Fungi from the Common Walnut and Their in Vitro Antagonistic Activity against Ophiognomonia leptostyla. Biologia 2023, 78, 361–371. [Google Scholar] [CrossRef]
  156. Ahmad, T.; Xing, F.; Nie, C.; Cao, C.; Xiao, Y.; Yu, X.; Moosa, A.; Liu, Y. Biocontrol Potential of Lipopeptides Produced by the Novel Bacillus subtilis Strain Y17B against Postharvest Alternaria Fruit Rot of Cherry. Front. Microbiol. 2023, 14, 689. [Google Scholar] [CrossRef]
  157. Diabankana, R.G.C.; Shulga, E.U.; Validov, S.Z.; Afordoanyi, D.M. Genetic Characteristics and Enzymatic Activities of Bacillus velezensis KS04AU as a Stable Biocontrol Agent against Phytopathogens. Int. J. Plant Biol. 2022, 13, 201–222. [Google Scholar] [CrossRef]
  158. Costa, A.; Corallo, B.; Amarelle, V.; Stewart, S.; Pan, D.; Tiscornia, S.; Fabiano, E. Paenibacillus sp. Strain UY79, Isolated from a Root Nodule of Arachis Villosa, Displays a Broad Spectrum of Antifungal Activity. Appl. Environ. Microbiol. 2022, 88, e01645-21. [Google Scholar] [CrossRef]
  159. Matilla, M.A.; Monson, R.E.; Murphy, A.; Schicketanz, M.; Rawlinson, A.; Duncan, C.; Mata, J.; Leeper, F.; Salmond, G.P.C. Solanimycin: Biosynthesis and Distribution of a New Antifungal Antibiotic Regulated by Two Quorum-Sensing Systems. mBio 2022, 13, 22. [Google Scholar] [CrossRef]
  160. Pandin, C.; Le Coq, D.; Deschamps, J.; Védie, R.; Rousseau, T.; Aymerich, S.; Briandet, R. Complete Genome Sequence of Bacillus velezensis QST713: A Biocontrol Agent That Protects Agaricus bisporus Crops against the Green Mould Disease. J. Biotechnol. 2018, 278, 10–19. [Google Scholar] [CrossRef]
  161. Palazzini, J.M.; Dunlap, C.A.; Bowman, M.J.; Chulze, S.N. Bacillus velezensis RC 218 as a Biocontrol Agent to Reduce Fusarium Head Blight and Deoxynivalenol Accumulation: Genome Sequencing and Secondary Metabolite Cluster Profiles. Microbiol. Res. 2016, 192, 30–36. [Google Scholar] [CrossRef]
  162. Korangi Alleluya, V.; Argüelles Arias, A.; Ribeiro, B.; De Coninck, B.; Helmus, C.; Delaplace, P.; Ongena, M. Bacillus Lipopeptide-Mediated Biocontrol of Peanut Stem Rot Caused by Athelia rolfsii. Front. Plant. Sci. 2023, 14, 1069971. [Google Scholar] [CrossRef]
  163. Al-Mutar, D.M.K.; Alzawar, N.S.A.; Noman, M.; Azizullah; Li, D.; Song, F. Suppression of Fusarium wilt in Watermelon by Bacillus smyloliquefaciens DHA55 through Extracellular Production of Antifungal Lipopeptides. J. Fungi 2023, 9, 336. [Google Scholar] [CrossRef]
  164. ALTRÃO, C.S. Characterization of Disease Suppression Activity of Bacillus Cyclic Lipopeptide Depending on the Induced Disease Resistance in Plant. Ph.D. Thesis, Tokyo University of Agriculture, Tokyo, Japan, 2022. [Google Scholar]
  165. Höfte, M. The Use of Pseudomonas spp. as Bacterial Biocontrol Agents to Control Plant Diseases. Burleigh Dodds Ser. Agric. Sci. 2021, 301–374. [Google Scholar] [CrossRef]
  166. Hoff, G.; Arias, A.A.; Boubsi, F.; Pršic, J.; Meyer, T.; Ibrahim, H.M.M.; Steels, S.; Luzuriaga, P.; Legras, A.; Franzil, L.; et al. Surfactin Stimulated by Pectin Molecular Patterns and Root Exudates Acts as a Key Driver of the Bacillus-Plant Mutualistic Interaction. mBio 2021, 12, e01774-21. [Google Scholar] [CrossRef]
  167. Laird, M.; Piccoli, D.; Weselowski, B.; McDowell, T.; Renaud, J.; MacDonald, J.; Yuan, Z.C. Surfactin-Producing Bacillus velezensis 1B-23 and Bacillus sp. 1D-12 Protect Tomato against Bacterial Canker Caused by Clavibacter michiganensis subsp. Michiganensis. J. Plant Pathol. 2020, 102, 451–458. [Google Scholar] [CrossRef]
  168. Abdallah, D.B.; Krier, F.; Jacques, P.; Tounsi, S.; Frikha-Gargouri, O. Agrobacterium Tumefaciens C58 Presence Affects Bacillus velezensis 32a Ecological Fitness in the Tomato Rhizosphere. Environ. Sci. Pollut. Res. 2020, 27, 28429–28437. [Google Scholar] [CrossRef]
  169. Wu, J.J.; Huang, J.W.; Deng, W.L. Phenylacetic Acid and Methylphenyl Acetate From the Biocontrol Bacterium Bacillus mycoides BM02 Suppress Spore Germination in Fusarium oxysporum f. sp. lycopersici. Front. Microbiol. 2020, 11, 1–12. [Google Scholar] [CrossRef]
  170. Azizoglu, U.; Yilmaz, N.; Simsek, O.; Ibal, J.C.; Tagele, S.B.; Shin, J.-H. The Fate of Plant Growth-Promoting Rhizobacteria in Soilless Agriculture: Future Perspectives. 3 Biotech. 2021, 11, 1–13. [Google Scholar] [CrossRef]
  171. Singh, G.; Biswas, D.R.; Marwaha, T.S. Mobilization of Potassium from Waste Mica by Plant Growth Promoting Rhizobacteria and Its Assimilation by Maize (Zea Mays) and Wheat (Triticum aestivum L.): A Hydroponics Study under Phytotron Growth Chamber. J. Plant Nutr. 2010, 33, 1236–1251. [Google Scholar] [CrossRef]
  172. Strigul, N.S.; Kravchenko, L.V. Mathematical Modeling of PGPR Inoculation into the Rhizosphere. Environ. Model. Softw. 2006, 21, 1158–1171. [Google Scholar] [CrossRef]
  173. Basu, A.; Prasad, P.; Das, S.N.; Kalam, S.; Sayyed, R.Z.; Reddy, M.S.; El Enshasy, H. Plant Growth Promoting Rhizobacteria (PGPR) as Green Bioinoculants: Recent Developments, Constraints, and Prospects. Sustainability 2021, 13, 1140. [Google Scholar] [CrossRef]
  174. Orhan, F. Alleviation of Salt Stress by Halotolerant and Halophilic Plant Growth-Promoting Bacteria in Wheat (Triticum aestivum). Braz. J. Microbiol. 2016, 47, 621–627. [Google Scholar] [CrossRef] [Green Version]
  175. Moncada, A.; Vetrano, F.; Miceli, A. Alleviation of Salt Stress by Plant Growth-Promoting Bacteria in Hydroponic Leaf Lettuce. Agronomy 2020, 10, 1523. [Google Scholar] [CrossRef]
  176. Prajapati, K.; Modi, H. Growth Promoting Effect of Potassium Solubilizing Enterobacter Hormaechei (KSB-8) on Cucumber (Cucumis sativus) under Hydroponic Conditions. Int. J. Adv. Res. Biol. Sci. 2016, 3, 168–173. [Google Scholar]
  177. Suzuki, W.; Sugawara, M.; Miwa, K.; Morikawa, M. Plant Growth-Promoting Bacterium Acinetobacter calcoaceticus P23 Increases the Chlorophyll Content of the Monocot Lemna Minor (Duckweed) and the Dicot Lactuca Sativa (Lettuce). J. Biosci. Bioeng. 2014, 118, 41–44. [Google Scholar] [CrossRef]
  178. Murgese, P.; Santamaria, P.; Leoni, B.; Crecchio, C. Ameliorative Effects of PGPB on Yield, Physiological Parameters, and Nutrient Transporter Genes Expression in Barattiere (Cucumis melo L.). J. Soil. Sci. Plant. Nutr. 2020, 20, 784–793. [Google Scholar] [CrossRef]
  179. Issifu, M.; Songoro, E.K.; Onguso, J.; Ateka, E.M.; Ngumi, V.W. Potential of Pseudarthrobacter Chlorophenolicus BF2P4-5 as a Biofertilizer for the Growth Promotion of Tomato Plants. Bacteria 2022, 1, 191–206. [Google Scholar] [CrossRef]
  180. Kim, J.; Woo, O.-G.; Bae, Y.; Keum, H.L.; Chung, S.; Sul, W.J.; Lee, J.-H. Enhanced Drought and Salt Stress Tolerance in Arabidopsis by Flavobacterium Crocinum HYN0056 T. J. Plant Biol. 2020, 63, 63–71. [Google Scholar] [CrossRef]
  181. Li, X.; Yan, J.; Li, D.; Jiang, Y.; Zhang, Y.; Wang, H.; Zhang, J.; Ahmed, T.; Li, B. Isolation and Molecular Characterization of Plant-Growth-Promoting Bacteria and Their Effect on Eggplant (Solanum Melongena) Growth. Agriculture 2021, 11, 1258. [Google Scholar] [CrossRef]
  182. Turan, M.; Ekinci, M.; Yildirim, E.; Güneş, A.; Karagöz, K.; Kotan, R.; Dursun, A. Plant Growth-Promoting Rhizobacteria Improved Growth, Nutrient, and Hormone Content of Cabbage (Brassica oleracea) Seedlings. Turk. J. Agric. For. 2014, 38, 327–333. [Google Scholar] [CrossRef]
  183. Abdalla, O.A.; Bibi, S.; Zhang, S. Application of Plant Growth-Promoting Rhizobacteria to Control Papaya Ringspot Virus and Tomato Chlorotic Spot Virus. Arch. Phytopathol. Plant Prot. 2017, 50, 584–597. [Google Scholar] [CrossRef]
  184. de Sousa, S.M.; de Oliveira, C.A.; Andrade, D.L.; de Carvalho, C.G.; Ribeiro, V.P.; Pastina, M.M.; Marriel, I.E.; de Paula Lana, U.G.; Gomes, E.A. Tropical Bacillus Strains Inoculation Enhances Maize Root Surface Area, Dry Weight, Nutrient Uptake and Grain Yield. J. Plant Growth Regul. 2021, 40, 867–877. [Google Scholar] [CrossRef]
  185. Yasmin, H.; Naeem, S.; Bakhtawar, M.; Jabeen, Z.; Nosheen, A.; Naz, R.; Keyani, R.; Mumtaz, S.; Hassan, M.N. Halotolerant Rhizobacteria Pseudomonas pseudoalcaligenes and Bacillus subtilis Mediate Systemic Tolerance in Hydroponically Grown Soybean (Glycine max L.) against Salinity Stress. PLoS ONE 2020, 15, e0231348. [Google Scholar] [CrossRef]
  186. Sepehri, M.; Khatabi, B. Combination of Siderophore-Producing Bacteria and Piriformospora indica Provides an Efficient Approach to Improve Cadmium Tolerance in Alfalfa. Microb. Ecol. 2021, 81, 717–730. [Google Scholar] [CrossRef]
Figure 1. Different types of NRPs and their application in agriculture, environment, food, and other industries.
Figure 1. Different types of NRPs and their application in agriculture, environment, food, and other industries.
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Figure 2. Structure of potential non-ribosomal compounds: (a) surfactin, (b) fengycin, and (c) iturin. R1, R2, and R3 exhibit 9 to 13, 11 to 14, and 11 to 14 carbon atoms, respectively.
Figure 2. Structure of potential non-ribosomal compounds: (a) surfactin, (b) fengycin, and (c) iturin. R1, R2, and R3 exhibit 9 to 13, 11 to 14, and 11 to 14 carbon atoms, respectively.
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Figure 3. Illustration of synthesis of NRPS in three steps as designated by three domains, namely initiation, elongation, and termination domains. The illustration has been adapted from Agrawal et al., 2017 [78].
Figure 3. Illustration of synthesis of NRPS in three steps as designated by three domains, namely initiation, elongation, and termination domains. The illustration has been adapted from Agrawal et al., 2017 [78].
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Figure 4. Strategies for isolation and characterization of non-ribosomal peptides from plant-growth-promoting bacteria.
Figure 4. Strategies for isolation and characterization of non-ribosomal peptides from plant-growth-promoting bacteria.
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Table 1. NRPs compounds against the bacterial plant pathogen biocontrol.
Table 1. NRPs compounds against the bacterial plant pathogen biocontrol.
S. No.Source OrganismCompoundAssessment MethodPlant-PathogenDisease CausedReference
1B. porteri HB1.4B
Brevibacillus RS1.1
Brevibacillus DP1.3A
Brevibacillus HB2.2
Uncharacterized NRPs and NRP-PK hybrids. Antagonist activity was identified through in vitro antibacterial activity and gene clusters were identified after whole-genome sequencing, analysis, and annotations Clavibacter michiganensisBacterial wilt and canker of tomato[131]
2B. porteri HB1.1
Brevibacillus DP1.3A
Xanthomonas campestrisblack rot in cruciferous[131]
3B. subtilis TY-1surfactin, bacillibactin, and fengycinIdentified using AntiSMASHRalstonia solanacearumBacterial wilt of tobacco[132]
4Pseudomonas strain CHA0orfamide ADirect contact inhibition, indirectly using supernatant assays
Whole-genome sequencing and AntiSMASH
R. solanacearumbacterial wilt in a range of host plants, e.g., potato, tobacco, tomato[133]
5Sphingomonas, Pseudoxanthomonas and StenotrophomonasNot SpecifiedNPRS BGC enrichment was confirmed using metagenomic studies.
Pathogen inhibition was further confirmed in pot experiments
R. solanacearumbacterial wilt in a range of host plants, e.g., potato, tobacco, tomato[134]
6Gordonia sp. TD-4Not SpecifiedNPRS BGC enrichment was confirmed using metagenomic studies Not SpecifiedNot Specified[135]
7Pseudomonas strain CHA0orfamide ADirect contact inhibition, indirectly using supernatant assays.
Whole-genome sequencing and AntiSMASH
R. solanacearumbacterial wilt in a range of host plants, e.g., potato, tobacco, tomato[133]
8B. subtilis EH11
Paenibacillus sp. EDO6
B. endophyticus FH5
Surfactin, fengycin, bacillibactin, petrobactin, lichenysin, and bacillaene.In vitro inhibition assay of bacterial pathogens and NRP bio-clusters were confirmed by genome-based analysisErwinia carotovorasoft rot disease of potato, carrot, and cabbage[136]
9B. subtilis EH11
Paenibacillus sp. EDO6
B. endophyticus FH5
P. syringaebacterial blight and bacterial speck among several plants[136]
10Brevibacillus laterosporus MG64Bogorols K MIC = 4 μg/mL
X. campestris pv. campestris NCCB92058Black rot disease in crucifers[24]
Bogorols L MIC = 2 μg/mL
X. campestris pv. campestris NCCB92058
Brevibacillin MIC = 2 μg/mL
X. campestris pv. campestris NCCB92058
11Brevibacillin MIC = 2 μg/mL
X. translucens pv. graminis LMG587leaf streak in wheat and cereal crop.[24]
Bogorol L MIC = 8 μg/mL
P. syringae pv. tomato DC3000
12P. mediterranea Strain S58Fengycin, Crochelin A, Entolysin, Orfamide B, Siderophore, SyringomycinAntagonistic test and Disease control assay confirmed the biocontrol potential. NRPS BGCs were identified, encoding for NRPsP. syringae pv. tabaciWild fire, Angular leaf spot in Tobacco[137]
13Lysobacter enzymogenes LE16 surfactinantiSMASHP. syringae pv. tabacitobacco wildfire disease[138]
14B.safensis F4SurfactinMIC = 1.56 mg mL−1 (crude biosurfactant)Identified using HPLCP. savastanoiolive knot disease[139]
15SurfactinMIC = 3.125 mg mL−1 (crude biosurfactant)Identified using HPLCAgrobacterium tumefaciensCrown gall [139]
16B. amyloliquefaciens SQR9FengycinIn vitro inhibition assayP. syringae pv. tomato DC3000 (Studied on Arabidopsis)Model organism for studying plant–bacterial interactions. This strain can infect Arabidopsis too [123]
Table 2. NRP compounds and their action against fungal plant pathogen biocontrol.
Table 2. NRP compounds and their action against fungal plant pathogen biocontrol.
S. No.Source Organism NRP CompoundAssessment MethodPathogenDisease CausedReference
1B. velezensis 2211Bacillomycin D (bmyA), fengycin (fenB)
  • Direct Inhibition study
  • Gene expression of NRPS BGCs
Colletotrichum fructicolaThe causal agent of anthracnose and soft rot in avocado fruits[148]
2B. subtilis Strain UD1022-
  • Direct and indirect antifungal assay
  • NRP mutant strains (srfAC ¯, ppsB ¯, ppsB ¯, srfAC ¯, and sfp ¯) were used to validate the antagonism of the strain UD1022
Clarireedia jacksoniiDollar spot of the grass[149]
3B. subtilis Strain UD1022Surfactin
  • Direct antagonism by plate inhibition assay
  • spo0A_ (surfactin-encoding gene) mutated strain
Ascochyta medicaginicola StC 306-5Black stem of Alfalfa and Medicago truncatula. [150]
4Burkholderia vietnamiensis strain WPBOccidiofungin
  • Dual plate inhibition assay
  • In silico identification of NRPS BGCs
Gaeumannomyces graminis var. triticiTake all diseases, roots of grass and cereal plants[151]
5B. velezensis S141surfactin, bacilysin, and bacillomycin D
  • Dual culture assays
  • Transcriptomic analysis of genes encoding surfactin, bacilysin, and bacillomycin D
Cercospora canescensleaf spot disease of amaranth [152]
6Pseudomonas spp. SK2, and SK3Obafuorin and cupriachelin
  • Plate-based inhibition assay
  • In vitro tube assay with wheat plant
  • Whole-genome sequencing and antiSMASH
  • Extracted ion chromatograms (EIC) and detected by LC/MS
F. oxysporumyellowing, stunting, and death of seedlings and yellowing and stunting of older plants[153]
7Pseudomonas spp. SK2, and SK3Obafuorin and cupriachelin
  • Plate-based inhibition assay
  • In vitro tube assay with wheat plant
  • Whole-genome sequencing and antiSMASH
  • Extracted ion chromatograms (EIC) and detected by LC/MS
Verticillium dahliaeverticillium wilt causes the leaves to curl and discolor.[153]
8B. subtilis PTS-394Surfactin, Iturin, and Fengcyin
  • Plate-based inhibition assay
  • Biocontrol study on the plant was studied on pot and field too.
F. solanipepper root rot[154]
9Alternaria sp. CC-3 NRPS BGCs were identified
  • Direct antagonist study was conducted (52.5% inhibition)
  • Primer-based amplification
Ophiognomonia leptostylawalnut anthracnose or walnut black spot[155]
10B. subtilis strain Y17Bsurfactin
  • 61.3% inhibition on plate assay.
  • Primer-based amplification of BGCs and UPLC Q TOF mass spectrometry analysis
Alternaria alternataLeaf spots, rots, blights and affects other plant parts in over 380 host plants [156]
11Bacillus. velezensis KS04AU. Surfactin
  • confrontation assay of Petri plate, BGCs for surfactin were identified by antiSMASH
F. oxysporum f. sp. radicis-lycopersici ZUM2407 (Forl ZUM2407)Fusarium wilt disease in Tomatoes causes heavy loss[157]
12Paenibacillus sp. strain (UY79)fusaricidin B, tridecaptin,
  • Direct inhibition assay
  • Whole-genome sequencing, AntiSMASH
F. verticillioides A71.seedling blight, or stalk or ear rot in maize[158]
13Dickeya solani MK10Solanimycin
  • Direct inhibition assay
  • antiSMASH
V. dahliaeverticillium wilt in many host plants[159]
14B. subtilis (B. velezensis QST713)Ericin + NRPS
  • Biocontrol assay
  • antiSMASH
T. aggressivumgreen mold disease [160]
15Bacillus subtilis (B. velezensis RC 218)Iturin, Fengycin
  • Bioassay, LC-MS, whole-genome sequencing, antiSMASH3.0
F. graminearumFusarium head blight[161]
Table 3. NRP compounds and their potential application for biocontrol of plant pathogens in soilless agriculture (hydroponics).
Table 3. NRP compounds and their potential application for biocontrol of plant pathogens in soilless agriculture (hydroponics).
S. No.NRP CompoundSource of NRP (Only Bacteria) Pathogen Plant NameReference
1Purified surfactinB. velezensis GA1Athelia rolfsiiPeanut[162]
2Iturin, bacillomycin
D, surfactin, and fengycin
B. amyloliquefaciens
F. oxysporum f. sp. niveum (fon)Watermelon[163]
3Surfactin, Iturin ABacillus spp.P. syringae pv. maculicola MAFF 302783Cabbage[164]
4LokisinP. koreensis 2.74 (CBS 125413)Pythium ultimumTomato[165]
5SurfactinB. velezensisBotrytis cinereaTobacco[166]
6Surfactin A, surfactin B, Surfactin CB. velezenis 1B-23 or Bacillus sp. 1D-12Clavibacter michiganensis subsp. michiganensisTomato[167]
7SurfactinB. velezensis 32aAgrobacterium tumefaciens C58Tomato[168]
8Phenylacetic acid (PAA) and methylphenyl acetate (MPA)B. mycoides BM02F. oxysporum f. sp. lycopersici (Fol)Tomato[169]
Table 5. Commercial PGPB formulations and their bacterial ingredients.
Table 5. Commercial PGPB formulations and their bacterial ingredients.
Brand NamePGPB UsedManufacturerCountry of Origin
Taegro 2B. subtilis var. amyloliquefaciens Strain FZB24NovozymesDenmark
RhizolizerB. amyloliquefaciens along with a fungus Trichoderma harzianumLocus Agricultural SolutionsUnited States
LALGUARD M52 ODB. subtilisLallemand Plant CareCanada
RHIZOVITAL® 42B. amyloliquefaciensAndermattCanada
GeumanoControlNot DisclosedBio-lidePoland
CEASEB. subtilis strain QST 713BioWorks Inc.United States
Nutri-Life PlatformConsortium of Bacillus, Pseudomonas, and TrichodermaNutri-Tech SolutionsAustralia
Serenade® SOILBacillus subtilis QST 713BayerCanada
Subtilex®B. subtilis strain MBI 600BioglobalTurkey
Rizovital 42Bacillus amyloliquefaciensOrganic Crop Protectants (OCP)Australia
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Ranjan, A.; Rajput, V.D.; Prazdnova, E.V.; Gurnani, M.; Bhardwaj, P.; Sharma, S.; Sushkova, S.; Mandzhieva, S.S.; Minkina, T.; Sudan, J.; et al. Nature’s Antimicrobial Arsenal: Non-Ribosomal Peptides from PGPB for Plant Pathogen Biocontrol. Fermentation 2023, 9, 597.

AMA Style

Ranjan A, Rajput VD, Prazdnova EV, Gurnani M, Bhardwaj P, Sharma S, Sushkova S, Mandzhieva SS, Minkina T, Sudan J, et al. Nature’s Antimicrobial Arsenal: Non-Ribosomal Peptides from PGPB for Plant Pathogen Biocontrol. Fermentation. 2023; 9(7):597.

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Ranjan, Anuj, Vishnu D. Rajput, Evgeniya Valeryevna Prazdnova, Manisha Gurnani, Pallavi Bhardwaj, Shikha Sharma, Svetlana Sushkova, Saglara S. Mandzhieva, Tatiana Minkina, Jebi Sudan, and et al. 2023. "Nature’s Antimicrobial Arsenal: Non-Ribosomal Peptides from PGPB for Plant Pathogen Biocontrol" Fermentation 9, no. 7: 597.

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