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Antibiotics
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Synthetic Biology Brings New Opportunity for Antibiotics Discovery
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Synthetic Biology Brings New Opportunity for Antibiotics Discovery

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Biosynthesis and Combinatorial Approaches in Antimicrobial Discovery".

Deadline for manuscript submissions: closed (10 September 2022) | Viewed by 25257

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Yaojun Tong

E-Mail Website
Guest Editor
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
Interests: Crispr; microbiology; natural products; synthetic biology; cell factory
Prof. Dr. Zixin Deng

E-Mail Website
Guest Editor
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Interests: synthetic biology; natural products
Prof. Dr. Linquan Bai

E-Mail Website
Guest Editor
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
Interests: Biosynthesis of antibiotics

Special Issue Information

Dear Colleagues,

Though society is developing much more rapidly today than it did in the past, we are facing a complicated public health issue in the form of global drug shortages, and antimicrobials are unfortunately on that list. These shortages are caused by various issues, e.g., technological limitations, which have led to a drying up of the pipeline of antimicrobial development. Indeed, it has been decades since antibiotics with a completely novel mode of action were last delivered to the clinic. The limited availability of antibiotics, in addition to the rapid emergence of multidrug resistance, are putting us in a very dangerous position. Luckily, the advances of new technologies, especially biotechnologies, such as DNA sequencing, precise genome editing, system metabolic engineering, multiomics, synthetic biology, big data processing, and artificial intelligence are offering a great opportunity to develop better and efficient bioactive molecules, including next-generation antibiotics. Currently, various achievements and new discoveries from both academia and industry are taking place in the broad field of antibiotics, which reflects the fact that a new era is coming. As one of the most important driving forces, academia plays a critical role in drug discovery for a safer society, and thus, we would like to bring academia, industry, and clinic together in this Special Issue to report recent progress in antibiotics discovery.

Prof. Dr. Yaojun Tong
Prof. Dr. Zixin Deng
Prof. Dr. Linquan Bai
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. Antibiotics 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 2900 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

  • Antimicrobial
  • Antibiotics
  • Antivirus
  • Bioactive natural products
  • Multidrug resistance
  • Biosynthesis
  • Metabolic engineering
  • Synthetic biology
  • Advanced biotechnology
  • Microbial cell factory

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

3 pages, 177 KiB  
Editorial
Synthetic Biology Facilitates Antimicrobials Discovery
by Linquan Bai, Zixin Deng and Yaojun Tong
Antibiotics 2023, 12(3), 578; https://doi.org/10.3390/antibiotics12030578 - 15 Mar 2023
Viewed by 1401
Abstract
We are currently facing two big global challenges: antibiotics shortage and multidrug resistance [...] Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)

Research

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12 pages, 1501 KiB  
Article
Identification and Characterization of Genes Related to Ampicillin Antibiotic Resistance in Zymomonas mobilis
by Binan Geng, Xingyu Huang, Yalun Wu, Qiaoning He and Shihui Yang
Antibiotics 2022, 11(11), 1476; https://doi.org/10.3390/antibiotics11111476 - 25 Oct 2022
Cited by 2 | Viewed by 1845
Abstract
Antibiotics can inhibit or kill microorganisms, while microorganisms have evolved antibiotic resistance strategies to survive antibiotics. Zymomonas mobilis is an ideal industrial microbial chassis and can tolerate multiple antibiotics. However, the mechanisms of antibiotic resistance and genes associated with antibiotic resistance have not [...] Read more.
Antibiotics can inhibit or kill microorganisms, while microorganisms have evolved antibiotic resistance strategies to survive antibiotics. Zymomonas mobilis is an ideal industrial microbial chassis and can tolerate multiple antibiotics. However, the mechanisms of antibiotic resistance and genes associated with antibiotic resistance have not been fully analyzed and characterized. In this study, we investigated genes associated with antibiotic resistance using bioinformatic approaches and examined genes associated with ampicillin resistance using CRISPR/Cas12a−based genome−editing technology. Six ampicillin−resistant genes (ZMO0103, ZMO0893, ZMO1094, ZMO1650, ZMO1866, and ZMO1967) were identified, and five mutant strains ZM4∆0103, ZM4∆0893, ZM4∆1094, ZM4∆1650, and ZM4∆1866 were constructed. Additionally, a four−gene mutant ZM4∆ARs was constructed by knocking out ZMO0103, ZMO0893, ZMO1094, and ZMO1650 continuously. Cell growth, morphology, and transformation efficiency of mutant strains were examined. Our results show that the cell growth of ZM4∆0103 and ZM4∆ARs was significantly inhibited with 150 μg/mL ampicillin, and cells changed to a long filament shape from a short rod shape. Moreover, the transformation efficiencies of ZM4∆0103 and ZM4∆ARs were decreased. Our results indicate that ZMO0103 is the key to ampicillin resistance in Z. mobilis, and other ampicillin−resistant genes may have a synergetic effect with it. In summary, this study identified and characterized genes related to ampicillin resistance in Z. mobilis and laid a foundation for further study of other antibiotic resistance mechanisms. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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10 pages, 1471 KiB  
Article
Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in Streptomyces hygrospinosus var. Beijingensis
by Dashan Zhang, Junbo Wang, Yongjian Qiao, Baixin Lin, Zixin Deng, Lingxin Kong and Delin You
Antibiotics 2022, 11(11), 1463; https://doi.org/10.3390/antibiotics11111463 - 24 Oct 2022
Cited by 4 | Viewed by 1463
Abstract
Two new cyclodipeptide (CDP) derivatives (1–2) and another seven known cyclodipeptides (3–9) were isolated from Streptomyces 26D9-414 by the genome mining approach combined with genetic dereplication and the “one strain many compounds” (OSMAC) strategy. The structures of the new [...] Read more.
Two new cyclodipeptide (CDP) derivatives (1–2) and another seven known cyclodipeptides (3–9) were isolated from Streptomyces 26D9-414 by the genome mining approach combined with genetic dereplication and the “one strain many compounds” (OSMAC) strategy. The structures of the new CDPs were established on the basis of 1D- and 2D-NMR and comparative electronic circular dichroism (ECD) spectra analysis. The biosynthetic gene clusters (BGCs) for these CDPs were identified through antiSMASH analysis. The relevance between this cdp cluster and the identified nine CDPs was established by genetic interruption manipulation. The newly discovered natural compound 2 displayed comparable cytotoxicity against MDA-MB-231 and SW480 with that of cisplatin, a widely used chemotherapeutic agent for the treatment of various cancers. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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9 pages, 1500 KiB  
Communication
Genome Mining Discovery of a New Benzazepine Alkaloid Pseudofisnin A from the Marine Fungus Neosartorya pseudofischeri F27-1
by Xiao-Xin Xue, Lin Chen and Man-Cheng Tang
Antibiotics 2022, 11(10), 1444; https://doi.org/10.3390/antibiotics11101444 - 20 Oct 2022
Cited by 4 | Viewed by 1422
Abstract
l-Kynurenine (Kyn) is an intermediate in the kynurenine pathway and is also found to be a building block or biosynthetic precursor to bioactive natural products. Recent studies revealed that l-Kyn can be incorporated via nonribosomal peptide synthetase (NRPS) biosynthetic routes to [...] Read more.
l-Kynurenine (Kyn) is an intermediate in the kynurenine pathway and is also found to be a building block or biosynthetic precursor to bioactive natural products. Recent studies revealed that l-Kyn can be incorporated via nonribosomal peptide synthetase (NRPS) biosynthetic routes to generate 1-benzazepine-containing compounds, while 1-benzazepine is a pharmaceutically important scaffold that is rarely found in natural products. Using a core biosynthetic enzyme-guided genome-mining approach, we discovered a biosynthetic gene cluster from Neosartorya pseudofischeri and identified that it encodes for the biosynthesis of pseudofisnins, novel 1-benzazepine-containing compounds. The biosynthetic pathway of pseudofisnins was elucidated through in vivo and in vitro experiments. The methyltransferase PseC from the pathway was biochemically characterized to be an iterative methyltransferase that catalyzes off-NRPS line di-methylation on an amine group. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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24 pages, 6663 KiB  
Article
Synthesis, Spectroscopic, Chemical Characterizations, Anticancer Capacities against HepG-2, Antibacterial and Antioxidant Activities of Cefotaxime Metal Complexes with Ca(II), Cr(III), Zn(II), Cu(II) and Se(IV)
by Eman H. Al-Thubaiti, Samy M. El-Megharbel, Bander Albogami and Reham Z. Hamza
Antibiotics 2022, 11(7), 967; https://doi.org/10.3390/antibiotics11070967 - 19 Jul 2022
Cited by 6 | Viewed by 2044
Abstract
In this study, metal cefotaxime complexes of Ca(II), Cr(III), Cu(II), Zn(II), and Se(VI) were synthesized and characterized by elemental analysis, conductance measurements, IR, electronic spectra, magnetic measurements, 1HNMR, and XRD, as well as by scanning electron microscopy (SEM) and transmission electron microscopy [...] Read more.
In this study, metal cefotaxime complexes of Ca(II), Cr(III), Cu(II), Zn(II), and Se(VI) were synthesized and characterized by elemental analysis, conductance measurements, IR, electronic spectra, magnetic measurements, 1HNMR, and XRD, as well as by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The lower values for molar conductance refer to the nonelectrolyte nature of the complexes. The FTIR and 1H-NMR spectra for the metal complexes of cefotaxime proved that the free cefotaxime antibiotic ligand acted as a monoanionic tridentate ligand through the oxygen atoms of lactam carbonyl, the carboxylate group, and the nitrogen atoms of the amino group. From the magnetic measurements and electronic spectral data, octahedral structures were proposed for the Cr(III) and Se(VI) complexes, while the Cu(II) complex had tetragonal geometry. This study aimed to investigate the effects of cefotaxime and cefotaxime metal complexes on oxidative stress using antioxidant assays including DPPH, ORAC, FARAB, and ABTS, a metal chelation assay, as well as the inhibition of the viability of cancer cells (HepG-2). Regarding the antibacterial activity, the cefotaxime metal complexes were highly effective against both Bacillus subtilis and Escherichia coli. In conclusion, the cefotaxime metal complexes exhibited highly antioxidant activities. The cefotaxime metal complexes with Zn and Se inhibited HepG-2 cellular viability. Thus, the cefotaxime metal complexes elicited promising results as potent antioxidant and anticancer agents against HepG-2, with potent antibacterial activities at a much lower concentration. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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13 pages, 3028 KiB  
Article
Comparative Transcriptome-Based Mining of Genes Involved in the Export of Polyether Antibiotics for Titer Improvement
by Xian Liu, Yuanting Wu, Xiaojie Zhang, Qianjin Kang, Yusi Yan and Linquan Bai
Antibiotics 2022, 11(5), 600; https://doi.org/10.3390/antibiotics11050600 - 29 Apr 2022
Cited by 3 | Viewed by 1753
Abstract
The anti-coccidiosis agent salinomycin is a polyether antibiotic produced by Streptomyces albus BK3-25 with a remarkable titer of 18 g/L at flask scale, suggesting a highly efficient export system. It is worth identifying the involved exporter genes for further titer improvement. In this [...] Read more.
The anti-coccidiosis agent salinomycin is a polyether antibiotic produced by Streptomyces albus BK3-25 with a remarkable titer of 18 g/L at flask scale, suggesting a highly efficient export system. It is worth identifying the involved exporter genes for further titer improvement. In this study, a titer gradient was achieved by varying soybean oil concentrations in a fermentation medium, and the corresponding transcriptomes were studied. Comparative transcriptomic analysis identified eight putative transporter genes, whose transcription increased when the oil content was increased and ranked top among up-regulated genes at higher oil concentrations. All eight genes were proved to be positively involved in salinomycin export through gene deletion and trans-complementation in the mutants, and they showed constitutive expression in the early growth stage, whose overexpression in BK3-25 led to a 7.20–69.75% titer increase in salinomycin. Furthermore, the heterologous expression of SLNHY_0929 or SLNHY_1893 rendered the host Streptomyces lividans with improved resistance to salinomycin. Interestingly, SLNHY_0929 was found to be a polyether-specific transporter because the titers of monensin, lasalocid, and nigericin were also increased by 124.6%, 60.4%, and 77.5%, respectively, through its overexpression in the corresponding producing strains. In conclusion, a transcriptome-based strategy was developed to mine genes involved in salinomycin export, which may pave the way for further salinomycin titer improvement and the identification of transporter genes involved in the biosynthesis of other antibiotics. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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21 pages, 4634 KiB  
Article
Synthesis, Spectroscopic Studies for Five New Mg (II), Fe (III), Cu (II), Zn (II) and Se (IV) Ceftriaxone Antibiotic Drug Complexes and Their Possible Hepatoprotective and Antioxidant Capacities
by Samy M. El-Megharbel, Safa H. Qahl, Fatima S. Alaryani and Reham Z. Hamza
Antibiotics 2022, 11(5), 547; https://doi.org/10.3390/antibiotics11050547 - 20 Apr 2022
Cited by 6 | Viewed by 2176
Abstract
Magnesium, copper, zinc, iron and selenium complexes of ceftriaxone were prepared in a 1:1 ligand to metal ratio to investigate the ligational character of the antibiotic ceftriaxone drug (CFX). The complexes were found to have coordinated and hydrated water molecules, except for the [...] Read more.
Magnesium, copper, zinc, iron and selenium complexes of ceftriaxone were prepared in a 1:1 ligand to metal ratio to investigate the ligational character of the antibiotic ceftriaxone drug (CFX). The complexes were found to have coordinated and hydrated water molecules, except for the Se (IV) complex, which had only hydrated water molecules. The modes of chelation were explained depending on IR, 1HNMR and UV–Vis spectroscopies. The electronic absorption spectra and the magnetic moment values indicated that Mg (II), Cu (II), Zn (II), Fe (III) and Se (VI) complexes form a six-coordinate shape with a distorted octahedral geometry. Ceftriaxone has four donation sites through nitrogen from NH2 amino, oxygen from triazine, β-lactam carbonyl and carboxylate with the molecular formulas [Mg(CFX)(H2O)2]·4H2O, [Cu(CFX)(H2O)2]·3H2O, [Fe(CFX)(H2O)(Cl)]·5H2O, [Zn(CFX)(H2O)2]·6H2O and [Se(CFX)(Cl)2]·4H2O and acts as a tetradentate ligand towards the five metal ions. The morphological surface and particle size of ceftriaxone metal complexes were determined using SEM, TEM and X-ray diffraction. The thermal behaviors of the complexes were studied by the TGA(DTG) technique. This study investigated the effect of CFX and CFX metal complexes on oxidative stress and severe tissue injury in the hepatic tissues of male rats. Fifty-six male rats were tested: the first group received normal saline (1 mg/kg), the second group received CFX orally at a dose of 180 mg/kg, and the other treated groups received other CFX metal complexes at the same dose as the CFX-treated group. For antibacterial activity, CFX/Zn complex was highly effective against Streptococcus pneumoniae, while CFX/Se was highly effective against Staphylococcus aureus and Escherichia coli. In conclusion, successive exposure to CFX elevated hepatic reactive oxygen species (ROS) levels and lipid peroxidation final marker (MDA) and decreased antioxidant enzyme levels. CFX metal complex administration prevented liver injury, mainly suppressing excessive ROS generation and enhancing antioxidant defense enzymes and in male rats. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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15 pages, 1617 KiB  
Article
SspH, a Novel HATPase Family Regulator, Controls Antibiotic Biosynthesis in Streptomyces
by Xue Yang, Yanyan Zhang, Shanshan Li, Lan Ye, Xiangjing Wang and Wensheng Xiang
Antibiotics 2022, 11(5), 538; https://doi.org/10.3390/antibiotics11050538 - 19 Apr 2022
Cited by 4 | Viewed by 1723
Abstract
Streptomyces can produce a wealth of pharmaceutically valuable antibiotics and other bioactive compounds. Production of most antibiotics is generally low due to the rigorously controlled regulatory networks, in which global/pleiotropic and cluster-situated regulatory proteins coordinate with various intra- and extracellular signals. Thus, mining [...] Read more.
Streptomyces can produce a wealth of pharmaceutically valuable antibiotics and other bioactive compounds. Production of most antibiotics is generally low due to the rigorously controlled regulatory networks, in which global/pleiotropic and cluster-situated regulatory proteins coordinate with various intra- and extracellular signals. Thus, mining new antibiotic regulatory proteins, particularly the ones that are widespread, is essential for understanding the regulation of antibiotic biosynthesis. Here, in the biopesticide milbemycin producing strain Streptomyces bingchenggensis, a novel global/pleiotropic regulatory protein, SspH, a single domain protein containing only the HATPase domain, was identified as being involved in controlling antibiotic biosynthesis. The sspH overexpression inhibited milbemycin production by repressing the expression of milbemycin biosynthetic genes. The sspH overexpression also differentially influenced the expression of various antibiotic biosynthetic core genes. Site-directed mutagenesis revealed that the HATPase domain was essential for SspH’s function, and mutation of the conserved amino acid residues N54A and D84A led to the loss of SspH function. Moreover, cross-overexpression experiments showed that SspH and its orthologs, SCO1241 from Streptomyces coelicolor and SAVERM_07097 from Streptomyces avermitilis, shared identical functionality, and all exerted a positive effect on actinorhodin production but a negative effect on avermectin production, indicating that SspH-mediated differential control of antibiotic biosynthesis may be widespread in Streptomyces. This study extended our understanding of the regulatory network of antibiotic biosynthesis and provided effective targets for future antibiotic discovery and overproduction. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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Review

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26 pages, 7261 KiB  
Review
Antifungal and Immunomodulatory Ingredients from Traditional Chinese Medicine
by Hua Zhong, Lei Han, Ren-Yi Lu and Yan Wang
Antibiotics 2023, 12(1), 48; https://doi.org/10.3390/antibiotics12010048 - 28 Dec 2022
Cited by 3 | Viewed by 3675
Abstract
Fungal infections have become a growing public health challenge due to the clinical transmission of pathogenic fungi. The currently available antifungal drugs leave very limited choices for clinical physicians to deal with such situation, not to mention the long-standing problems of emerging drug [...] Read more.
Fungal infections have become a growing public health challenge due to the clinical transmission of pathogenic fungi. The currently available antifungal drugs leave very limited choices for clinical physicians to deal with such situation, not to mention the long-standing problems of emerging drug resistance, side effects and heavy economic burdens imposed to patients. Therefore, new antifungal drugs are urgently needed. Screening drugs from natural products and using synthetic biology strategies are very promising for antifungal drug development. Chinese medicine is a vast library of natural products of biologically active molecules. According to traditional Chinese medicine (TCM) theory, preparations used to treat fungal diseases usually have antifungal and immunomodulatory functions. This suggests that if antifungal drugs are used in combination with immunomodulatory drugs, better results may be achieved. Studies have shown that the active components of TCM have strong antifungal or immunomodulatory effects and have broad application prospects. In this paper, the latest research progress of antifungal and immunomodulatory components of TCM is reviewed and discussed, hoping to provide inspiration for the design of novel antifungal compounds and to open up new horizons for antifungal treatment strategies. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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32 pages, 7453 KiB  
Review
Biosynthesis Investigations of Terpenoid, Alkaloid, and Flavonoid Antimicrobial Agents Derived from Medicinal Plants
by Wenqian Huang, Yingxia Wang, Weisheng Tian, Xiaoxue Cui, Pengfei Tu, Jun Li, Shepo Shi and Xiao Liu
Antibiotics 2022, 11(10), 1380; https://doi.org/10.3390/antibiotics11101380 - 09 Oct 2022
Cited by 18 | Viewed by 3691
Abstract
The overuse of antibiotics in the past decades has led to the emergence of a large number of drug-resistant microorganisms. In recent years, the infection rate caused by multidrug-resistant microorganisms has been increasing, which has become one of the most challenging problems in [...] Read more.
The overuse of antibiotics in the past decades has led to the emergence of a large number of drug-resistant microorganisms. In recent years, the infection rate caused by multidrug-resistant microorganisms has been increasing, which has become one of the most challenging problems in modern medicine. Plant-derived secondary metabolites and their derivatives have been identified to display significant antimicrobial abilities with good tolerance and less adverse side effects, potentially having different action mechanisms with antibiotics of microbial origin. Thus, these phyto-antimicrobials have a good prospect in the treatment of multidrug-resistant microorganisms. Terpenoids, alkaloids, and flavonoids made up the predominant part of the currently reported phytochemicals with antimicrobial activities. Synthetic biology research around these compounds is one of the hotspot fields in recent years, which not only has illuminated the biosynthesis pathways of these phyto-antimicrobials but has also offered new methods for their production. In this review, we discuss the biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents—using artemisinin and oleanolic acid (terpenoids), berberine and colchicine (alkaloids), and baicalin (flavonoids) as examples—around their antimicrobial action mechanisms, biosynthesis pathway elucidation, key enzyme identification, and heterologous production, in order to provide useful hints for plant-derived antimicrobial agent discovery and development. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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17 pages, 4178 KiB  
Review
Diverse Metabolites and Pharmacological Effects from the Basidiomycetes Inonotus hispidus
by Zhen-xin Wang, Xi-long Feng, Chengwei Liu, Jin-ming Gao and Jianzhao Qi
Antibiotics 2022, 11(8), 1097; https://doi.org/10.3390/antibiotics11081097 - 12 Aug 2022
Cited by 23 | Viewed by 2594 | Correction
Abstract
Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived [...] Read more.
Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived from I. hispidus and their biological activities have been discovered and investigated. Structurally, these compounds are mainly polyphenols and triterpenoids, which have anticancer, anti-inflammatory, antioxidant, antimicrobial, and enzyme inhibitor activities. Here, the secondary metabolites derived from I. hispidus and their activities were systematically and comprehensively classified and summarized, and the biosynthetic pathway of stylylpyrones was deduced and analyzed further. This review contributes to our understanding of I. hispidus and will help with research into natural product chemistry, pharmacology, and the biosynthesis of I. hispidus metabolites. According to this review, I. hispidus could be a promising source of bioactive compounds for health promotion and the development of functional foods. Full article
(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)
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