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Going Further with Microbial Secondary Metabolites and Biotechnology

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 24681

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Dr. Mireille Fouillaud

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Laboratory of Chemistry and Biotechnology of Natural Products, Faculty of Science and Technology, University of La Réunion, 15 Avenue René Cassin, CS 92003, CEDEX 09, 97744 Saint-Denis, France
Interests: microbiology; biotechnology; specialized metabolites; fermentations; pigments
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Laurent Dufossé

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Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments, ESIROI Département Agroalimentaire, Université de La Réunion, 2 rue Joseph Wetzell, F‐97490 Sainte‐Clotilde, La Réunion, France
Interests: sustainable textile; microbial biotechnology; microbial production of pigments and colorants; fermentation; bioprocess engineering and fermentation technology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is now clear for researchers that microorganisms are keystones in the evolution of global research, and thus in the evolution of human society. Microbes’ structures, productions or manipulations are much easier compared to complex organisms, and thus, exploiting their skills to improve our daily lives is a royal road.

New and complex tools in biotechnologies (biotools, bioprocesses, omics, etc.) have been widely used to initiate innovations based on microbial compounds dedicated to pharmaceutical, nutraceutical, or food industries. Accumulated knowledge now enables incredible advances on multiple aspects of microbial capacities and their use.

At an era of easy access to global scientific results, through worldwide networks and search engines, one of the factors limiting the speed of scientific advances is the mass of accessible data and the reduced capacity of researchers to collect and synthesize. Gathering all scientific studies on a chosen topic is the first step of any research work but is time-consuming and undoubtedly slows down the progress of science.

Against this backdrop, we have chosen to extend the first Special Issue focused on microbial secondary metabolites and biotechnology (https://www.mdpi.com/journal/microorganisms/special_issues/microbial_secondary_metabolites_
biotechnology) in order to provide a springboard for scientists to go faster and further in their research.

This new Special Issue called “Going Further with Microbial Secondary Metabolites and Biotechnology” is open to review papers dealing with microbial secondary metabolites and related biotechnologies. The state of the art of specific aspects as well as broad overviews of the latest developments in theoretical and technological advances will be welcome. This topic will appeal to researchers interested in the screening of active or useful novel bioproducts, or in microbes’ metabolic investigations, as well as -omic sciences dedicated to microbial biotechnologies. Fermentation pathways, production processes, as well as microbial industrial technologies can be part of this Special Issue. This issue will offer insights into the global knowledge dedicated to microbial biotechnology providing bio-based components and especially secondary metabolites.

This Special Issue will propose foundations to go further and faster into the exploitation of the metabolic diversity of bacteria, fungi, microalgae or viruses, with the aim of boosting innovations in microbial biotechnologies.

Dr. Mireille Fouillaud
Prof. Dr. Laurent Dufossé
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

microbial secondary metabolites
biotechnology
microbial production
culture optimisation
microbial engineering
genetic engineering
metabolic engineering
applied microbiology

Published Papers (8 papers)

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Research

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15 pages, 5027 KiB

Open AccessArticle

The 4-α-Glucanotransferase AcbQ Is Involved in Acarbose Modification in Actinoplanes sp. SE50/110

by Sophia Nölting, Camilla März, Lucas Jacob, Marcus Persicke, Susanne Schneiker-Bekel and Jörn Kalinowski

Microorganisms 2023, 11(4), 848; https://doi.org/10.3390/microorganisms11040848 - 27 Mar 2023

Viewed by 1553

Abstract

The pseudo-tetrasaccharide acarbose, produced by Actinoplanes sp. SE50/110, is a α-glucosidase inhibitor used for treatment of type 2 diabetes patients. In industrial production of acarbose, by-products play a relevant role that complicates the purification of the product and reduce yields. Here, we report that the acarbose 4-α-glucanotransferase AcbQ modifies acarbose and the phosphorylated version acarbose 7-phosphate. Elongated acarviosyl metabolites (α-acarviosyl-(1,4)-maltooligosaccharides) with one to four additional glucose molecules were identified performing in vitro assays with acarbose or acarbose 7-phosphate and short α-1,4-glucans (maltose, maltotriose and maltotetraose). High functional similarities to the 4-α-glucanotransferase MalQ, which is essential in the maltodextrin pathway, are revealed. However, maltotriose is a preferred donor and acarbose and acarbose 7-phosphate, respectively, serve as specific acceptors for AcbQ. This study displays the specific intracellular assembly of longer acarviosyl metabolites catalyzed by AcbQ, indicating that AcbQ is directly involved in the formation of acarbose by-products of Actinoplanes sp. SE50/110. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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27 pages, 4409 KiB

Open AccessArticle

Prioritization of Microorganisms Isolated from the Indian Ocean Sponge Scopalina hapalia Based on Metabolomic Diversity and Biological Activity for the Discovery of Natural Products

by Alexandre Le Loarer, Rémy Marcellin-Gros, Laurent Dufossé, Jérôme Bignon, Michel Frédérich, Allison Ledoux, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Anne Gauvin-Bialecki and Mireille Fouillaud

Microorganisms 2023, 11(3), 697; https://doi.org/10.3390/microorganisms11030697 - 08 Mar 2023

Cited by 2 | Viewed by 1762

Abstract

Despite considerable advances in medicine and technology, humanity still faces many deadly diseases such as cancer and malaria. In order to find appropriate treatments, the discovery of new bioactive substances is essential. Therefore, research is now turning to less frequently explored habitats with exceptional biodiversity such as the marine environment. Many studies have demonstrated the therapeutic potential of bioactive compounds from marine macro- and microorganisms. In this study, nine microbial strains isolated from an Indian Ocean sponge, Scopalina hapalia, were screened for their chemical potential. The isolates belong to different phyla, some of which are already known for their production of secondary metabolites, such as the actinobacteria. This article aims at describing the selection method used to identify the most promising microorganisms in the field of active metabolites production. The method is based on the combination of their biological and chemical screening, coupled with the use of bioinformatic tools. The dereplication of microbial extracts and the creation of a molecular network revealed the presence of known bioactive molecules such as staurosporin, erythromycin and chaetoglobosins. Molecular network exploration indicated the possible presence of novel compounds in clusters of interest. The biological activities targeted in the study were cytotoxicity against the HCT-116 and MDA-MB-231 cell lines and antiplasmodial activity against Plasmodium falciparum 3D7. Chaetomium globosum SH-123 and Salinispora arenicola SH-78 strains actually showed remarkable cytotoxic and antiplasmodial activities, while Micromonospora fluostatini SH-82 demonstrated promising antiplasmodial effects. The ranking of the microorganisms as a result of the different screening steps allowed the selection of a promising strain, Micromonospora fluostatini SH-82, as a premium candidate for the discovery of new drugs. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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19 pages, 2373 KiB

Open AccessArticle

Antioxidant, Cytotoxic, and DNA Damage Protection Activities of Endophytic Fungus Pestalotiopsis neglecta Isolated from Ziziphus spina-christi Medicinal Plant

by Hibah I. Almustafa and Ramy S. Yehia

Microorganisms 2023, 11(1), 117; https://doi.org/10.3390/microorganisms11010117 - 01 Jan 2023

Cited by 3 | Viewed by 2240

Abstract

Fungal endophytes are friendly microorganisms that colonize plants and are important in the interactions between plants and their environment. They generate valuable secondary metabolites that are valuable to both plants and humans. Endophytic fungi with bioactivities were isolated from the leaves of the medicinal plant Ziziphus spina-christi. An efficient isolate was selected and identified as Pestalotiopsis neglecta based on nucleotide sequencing of the internal transcribed spacer region (ITS 1-5.8S-ITS 2) of the 18S rRNA gene (NCBI accession number OP529850); the 564 bp had 99 to 100% similarity with P. neglecta MH860161.1, AY682935.1, KP689121.1, and MG572407.1, according to the BLASTn analysis, following preliminary phytochemical and antifungal screening. The biological activities of this fungus’ crude ethyl acetate (EtOAc) extract were assessed. With an efficient radical scavenging activity against 2,2′-diphenyl-1-picrylhydrazyl and an IC₅₀ value of 36.6 µg mL⁻¹, P. neglecta extract has shown its potential as an antioxidant. Moreover, it displayed notable cytotoxic effects against MCF-7 (breast carcinoma, IC₅₀ = 22.4 µg mL⁻¹), HeLa (cervical carcinoma, IC₅₀ = 28.9 µg mL⁻¹) and HepG-2 (liver carcinoma, IC₅₀ = 28.9 µg mL⁻¹). At 10 µg mL⁻¹, EtOAc demonstrated significant DNA protection against hydroxyl radical-induced damage. Based on FT-IR and GC-MS spectral analysis, it was detected that the EtOAc of P. neglecta product contains multiple bioactive functional groups. Subsequently, this validated the features of major different potent compounds; tolycaine, 1H-pyrazol, 1,3,5-trimethyl-, eugenol, 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethyl), and bis(2-ethylhexyl) phthalate. Since these compounds are biologically relevant in various aspects, and distinct biological activities of fungal extract were acceptable in vitro, this suggests that endophytic fungus P. neglecta may be a viable source of bioactive natural products. This could be a good starting point for pharmaceutical applications. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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20 pages, 1442 KiB

Open AccessArticle

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

by Nsikelelo Allison Malinga, Nomfundo Nzuza, Tiara Padayachee, Puleng Rosinah Syed, Rajshekhar Karpoormath, Dominik Gront, David R. Nelson and Khajamohiddin Syed

Microorganisms 2022, 10(5), 871; https://doi.org/10.3390/microorganisms10050871 - 21 Apr 2022

Cited by 8 | Viewed by 1961

Abstract

Cytochrome P450 monooxygenases (CYPs/P450s) are heme thiolate proteins present in species across the biological kingdoms. By virtue of their broad substrate promiscuity and regio- and stereo-selectivity, these enzymes enhance or attribute diversity to secondary metabolites. Actinomycetes species are well-known producers of secondary metabolites, especially Salinispora species. Despite the importance of P450s, a comprehensive comparative analysis of P450s and their role in secondary metabolism in Salinispora species is not reported. We therefore analyzed P450s in 126 strains from three different species Salinispora arenicola, S. pacifica, and S. tropica. The study revealed the presence of 2643 P450s that can be grouped into 45 families and 103 subfamilies. CYP107 and CYP125 families are conserved, and CYP105 and CYP107 families are bloomed (a P450 family with many members) across Salinispora species. Analysis of P450s that are part of secondary metabolite biosynthetic gene clusters (smBGCs) revealed Salinispora species have an unprecedented number of P450s (1236 P450s-47%) part of smBGCs compared to other bacterial species belonging to the genera Streptomyces (23%) and Mycobacterium (11%), phyla Cyanobacteria (8%) and Firmicutes (18%) and the classes Alphaproteobacteria (2%) and Gammaproteobacteria (18%). A peculiar characteristic of up to six P450s in smBGCs was observed in Salinispora species. Future characterization Salinispora species P450s and their smBGCs have the potential for discovering novel secondary metabolites. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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17 pages, 2992 KiB

Open AccessArticle

Interacting Environmental Stress Factors Affect Metabolomics Profiles in Stored Naturally Contaminated Maize

by Esther Garcia-Cela, Michael Sulyok, Carol Verheecke-Vaessen, Angel Medina, Rudolf Krska and Naresh Magan

Microorganisms 2022, 10(5), 853; https://doi.org/10.3390/microorganisms10050853 - 20 Apr 2022

Cited by 2 | Viewed by 1759

Abstract

There is interest in understanding the relationship between naturally contaminated commodities and the potential for the production of different useful and toxic secondary metabolites (SMs). This study examined the impact of interacting abiotic stress parameters of water availability and temperature of stored naturally contaminated maize on the SM production profiles. Thus, the effect of steady-state storage water activity (a_w; 0.80–0.95) and temperature (20–35 °C) conditions on SM production patterns in naturally contaminated maize was examined. The samples were analysed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to evaluate (a) the total number of known SMs, (b) their concentrations, and (c) changes under two-way interacting environmental stress conditions. A total of 151 metabolites were quantified. These included those produced by species of the Aspergillus, Fusarium and Penicillium genera and other unspecified ones by other fungi or bacteria. There were significant differences in the numbers of SMs produced under different sets of interacting environmental conditions. The highest total number of SMs (80+) were present in maize stored at 20–25 °C and 0.95 a_w. In addition, there was a gradation of SM production with the least number of SMs (20–30) produced under the driest conditions of 0.80 a_w at 20–30 °C. The only exception was at 35 °C, where different production patterns occurred. There were a total of 38 Aspergillus-related SMs, with most detected at >0.85 a_w, regardless of the temperature in the 50–500 ng/g range. For Fusarium-related SMs, the pattern was different, with approx. 10–12 SMs detected under all a_w × temperature conditions with >50% produced at 500 ng/g. A total of 40–45 Penicillium-related SMs (50–500 ng/g) were detected in the stored maize but predominantly at 20–25 °C and 0.95 a_w. Fewer numbers of SMs were found under marginal interacting abiotic stress storage conditions in naturally contaminated maize. There were approx. eight other known fungal SM present, predominantly in low concentrations (<50 ng/g), regardless of interacting abiotic conditions. Other unspecified SMs present consisted of <20 in low concentrations. The effect of interacting abiotic stress factors for the production of different suites of SMs to take account of the different ecological niches of fungal genera may be beneficial for identifying biotechnologically useful SMs. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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14 pages, 5340 KiB

Open AccessArticle

The Exploitation of a Hempseed Byproduct to Produce Flavorings and Healthy Food Ingredients by a Fermentation Process

by Lorenzo Nissen, Flavia Casciano, Elena Babini and Andrea Gianotti

Microorganisms 2021, 9(12), 2418; https://doi.org/10.3390/microorganisms9122418 - 23 Nov 2021

Cited by 5 | Viewed by 1904

Abstract

Following the One Health principles in food science, the challenge to valorize byproducts from the industrial sector is open. Hemp (Cannabis sativa subsp. sativa) is considered an important icon of sustainability and as an alternative food source. Hemp seed bran, in particular, is a byproduct of industrial hemp seed processing, which is not yet valorized. The success, and a wider market diffusion of hemp seed for food applications, is hindered by its unpleasant taste, which is produced by certain compounds that generally overwhelm the pleasant bouquet of the fresh product. This research concerns the exploration of hemp seed bran through fermentation using beneficial lactobacilli, focusing on the sensorial and bioactive traits of the products when they are subjected to bacterial transformation. By studying of the aromatic profile formation during the fermentation process the aim was to modulate it in order to reduce off-odors without affecting the presence of healthy volatile organic compounds (VOCs). Applying multivariate analyses, it was possible to target the contribution of processing parameters to the generation of flavoring and bioactive compounds. To conclude, the fermentation process proposed was able to reduce unpleasant VOCs, whilst at the same time keeping the healthy ones, and it also improved nutritional quality, depending on time and bacterial starters. The fermentation proposed was a sustainable biotechnological approach that fitted perfectly with the valorization of hemp byproducts from the perspective of a green-oriented industrial process that avoids synthetic masking agents. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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19 pages, 1370 KiB

Open AccessReview

Bacterial Pigments and Their Multifaceted Roles in Contemporary Biotechnology and Pharmacological Applications

by Himani Agarwal, Sneh Bajpai, Arti Mishra, Isha Kohli, Ajit Varma, Mireille Fouillaud, Laurent Dufossé and Naveen Chandra Joshi

Microorganisms 2023, 11(3), 614; https://doi.org/10.3390/microorganisms11030614 - 28 Feb 2023

Cited by 7 | Viewed by 8072

Abstract

Synthetic dyes and colourants have been the mainstay of the pigment industry for decades. Researchers are eager to find a more environment friendly and non-toxic substitute because these synthetic dyes have a negative impact on the environment and people’s health. Microbial pigments might be an alternative to synthetic pigments. Microbial pigments are categorized as secondary metabolites and are mainly produced due to impaired metabolism under stressful conditions. These pigments have vibrant shades and possess nutritional and therapeutic properties compared to synthetic pigment. Microbial pigments are now widely used within the pharmaceuticals, food, paints, and textile industries. The pharmaceutical industries currently use bacterial pigments as a medicine alternative for cancer and many other bacterial infections. Their growing popularity is a result of their low cost, biodegradable, non-carcinogenic, and environmentally beneficial attributes. This audit article has made an effort to take an in-depth look into the existing uses of bacterial pigments in the food and pharmaceutical industries and project their potential future applications. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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18 pages, 607 KiB

Open AccessReview

Secondary Metabolites Produced by Plant Growth-Promoting Bacterial Endophytes

by Zareen Narayanan and Bernard R. Glick

Microorganisms 2022, 10(10), 2008; https://doi.org/10.3390/microorganisms10102008 - 11 Oct 2022

Cited by 27 | Viewed by 4021

Abstract

There is an increasing interest in the use of beneficial microorganisms as alternatives to chemically synthesized or plant-derived molecules to produce therapeutic agents. Bacterial endophytes are plant-associated microorganisms that can colonize different parts of living plants without causing any diseases. Diverse endophytic bacteria possess the ability to synthesize a wide range of secondary metabolites with unique chemical structures that have been exploited for their anti-microbial, antiviral, anti-cancer, and anti-inflammatory properties. Additionally, production of these bioactive compounds can also benefit the host plant as they may play a significant role in a plant’s interaction with the environment for adaptation and defense. As a result of their significant impact as curative compounds or as precursors to produce new drugs, the biotechnological possibilities of secondary metabolites derived from endophytic bacteria are immense. Full article

(This article belongs to the Special Issue Going Further with Microbial Secondary Metabolites and Biotechnology)

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