Bacterial Secondary Metabolite Biosynthesis and Application for Biopharmaceutical and Bioengineering

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Microbiology and Ecological Metabolomics".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 5174

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School of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China
Interests: marine drug leads; efficient discovery; biosynthesis; fermentation preparation
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Special Issue Information

Dear Colleagues,

Bacterial natural products (NPs) are some of the most important sources of therapeutic agents. These NP-based drugs have made a tremendous contribution to human health throughout the world since they constitute half of the pharmaceuticals on the market today. However, the emerging and re-emerging infectious diseases (e.g., drug-resistant pathogens, coronavirus variants) pose complex and serious challenges to the global public health and the need for new antibiotics is highly urgent. In the past two decades,  bacterial NPs have greatly decreased. Fortunately, the application of new interdisciplinary approaches (e.g., genome mining and shuffling, metabolomics, ribosome engineering, heterologous expression) has substantially improved our ability to discover and develop novel functional biomolecules from these microbes and reinvigorated interest in natural product research in recent years.

This Special Issue welcomes both fundamental research papers and critical review works in the most recent and innovative developments of bacterial NP biosynthesis and application for biopharmaceutical and bioengineering. We sincerely wish that this issue can collect groundbreaking contributions in this field.

Prof. Dr. Huawei Zhang
Guest Editor

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Keywords

  • new bacterial NP discovery and biosynthetic analysis
  • antibiotic biosynthesis
  • extending metabolite diversity
  • genome mining and metabolomics
  • gene characterization and heteroexpression
  • activation of cryptic gene cluster of secondary metabolite
  • enhancement of valuable metabolite production

Published Papers (2 papers)

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Research

8 pages, 2364 KiB  
Article
Comparative Transcriptome Analysis of Two Chrysomycin-Producing Wild-Type and Mutant Strains of Streptomyces sp. 891
by Wangjie Zhu, Xinwei Pei, Xiaoyu Chen, You Wu, Fuhang Song and Huawei Zhang
Metabolites 2022, 12(12), 1170; https://doi.org/10.3390/metabo12121170 - 24 Nov 2022
Cited by 2 | Viewed by 1117
Abstract
Chrysomycin A (CA), a promising antibiotic agent, usually coexists with two analog chrysomycins B (CB) and C (CC) produced by several wild-type (WT) Streptomyces strains. With the aim to increase CA production, UV mutagenesis-based breeding had been employed on a marine-derived strain Streptomyces [...] Read more.
Chrysomycin A (CA), a promising antibiotic agent, usually coexists with two analog chrysomycins B (CB) and C (CC) produced by several wild-type (WT) Streptomyces strains. With the aim to increase CA production, UV mutagenesis-based breeding had been employed on a marine-derived strain Streptomyces sp. 891 in our previous study and afforded an improved strain 891-B6 with enhanced CA yield. By comparative transcriptome analysis, significant differences in chrysomycin BGC-related gene expression between the WT strain 891 and the mutant strain 891-B6 were unveiled in the current study. Among 25 up-regulated genes in mutant 891-B6, chryA, chryB, chryC, chryF, chryG, chryK, chryP, and chryQ, responsible for the biosynthesis of benzonaphthopyranone aglycone, and chryD, chryE, and chryU in charge of production of its deoxyglycoside, were characterized. Furthermore, the expression of genes chryOII, chryOIII, and chryOIV responsible for the formation of 8-vinyl in CA from 8-ethyl in CB were greatly enhanced in strain 891-B6. These findings provide molecular mechanisms for increased yield of CA and decreased yield of CB for mutant 891-B6, which has potential application in industrial CA production. Full article
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19 pages, 4381 KiB  
Article
Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study
by Said E. Desouky, Mohammed Abu-Elghait, Eman A. Fayed, Samy Selim, Basit Yousuf, Yasuhiro Igarashi, Basel A. Abdel-Wahab, Amnah Mohammed Alsuhaibani, Kenji Sonomoto and Jiro Nakayama
Metabolites 2022, 12(3), 246; https://doi.org/10.3390/metabo12030246 - 15 Mar 2022
Cited by 10 | Viewed by 3124
Abstract
Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In Staphylococcus aureus and Enterococcus faecalis, regulation of virulence genes’ expression occurs through the cyclic peptide-mediated accessory gene regulator (agr) and [...] Read more.
Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In Staphylococcus aureus and Enterococcus faecalis, regulation of virulence genes’ expression occurs through the cyclic peptide-mediated accessory gene regulator (agr) and its ortholog fsr quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria. The results indicated that four compounds, Phenalinolactones A–D, BU–4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus. On the other hand, Decatromicin A and B, Okilactomycin, Rishirilide A, Abyssomicin I, and Rebeccamycin selectively blocked the fsr quorum sensing system and the gelatinase production in E. faecalis at sub-lethal concentrations. Interestingly, Synerazol uniquely showed the capability to inhibit both fsr and agr quorum sensing systems. Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors. Full article
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