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Molecular Research on Microbial Natural Products
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Molecular Research on Microbial Natural Products

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 218

Special Issue Editor

Prof. Dr. Wenli Li

E-Mail Website
Guest Editor
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China
Interests: natural product biosynthesis; synthetic biology; enzymatic catalytic mechanisms; genome mining

Special Issue Information

Dear Colleagues,

Rapid advancements in molecular biology and biotechnology have revolutionized the discovery, characterization, and application of microbial natural products (MNPs), which exhibit diverse bioactivities with potential applications in medicine, agriculture, and industry. This Special Issue aims to provide a comprehensive overview of the latest research findings, methodologies, and challenges in the field of MNPs. The scope of this Special Issue will encompass, but not be limited to, the following areas: (1) biosynthetic gene cluster (BGC) analysis for decoding and engineering MNP pathways; (2) structural elucidation and bioactivity profiling, including antimicrobial, anticancer, and immunomodulatory properties; (3) metabolic engineering and synthetic biology strategies to optimize microbial hosts for scalable MNP production; (4) translational applications, such as therapeutic drug development and eco-friendly agricultural solutions; and (5) sustainable biomanufacturing practices to minimize environmental impacts. This Special Issue will serve as a platform for researchers to share cutting-edge knowledge and innovative solutions in the field of MNP research, fostering collaboration and advancing the frontiers of this dynamic area of science.

Prof. Dr. Wenli Li
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • microbial natural products
  • biosynthetic gene clusters
  • structural elucidation
  • metabolic engineering
  • synthetic biology
  • bioactivity profiling
  • sustainable biomanufacturing

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Published Papers (1 paper)

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Research

11 pages, 1103 KiB  
Article
Discovery of Tricyclic Aromatic Polyketides Reveals Hidden Chain-Length Flexibility in Type II Polyketide Synthases
by Yao Liu, Lijun Wang, Haiyan Wang, Yuchen Zhu, Jianing Sun, Boyang Ma, Lin Liu, Xunrui Bao, Jinwei Ren, Keqiang Fan, Liyan Wang, Xiao Li and Guohui Pan
Int. J. Mol. Sci. 2025, 26(16), 7801; https://doi.org/10.3390/ijms26167801 - 13 Aug 2025
Viewed by 123
Abstract
Type II polyketide synthases (PKSs) collectively generate polyketide intermediates of varying chain lengths, which undergo cyclization and further tailoring to produce structurally diverse aromatic polyketides. The length of the polyketide chain is a critical factor shaping the core scaffold of the final product. [...] Read more.
Type II polyketide synthases (PKSs) collectively generate polyketide intermediates of varying chain lengths, which undergo cyclization and further tailoring to produce structurally diverse aromatic polyketides. The length of the polyketide chain is a critical factor shaping the core scaffold of the final product. However, individual type II PKSs typically produce intermediates with a fixed chain length, thereby limiting the structural diversity accessible from a single biosynthetic system. In this study, we report the discovery of two pairs of novel tricyclic aromatic polyketides, varsomycin C/C′ and oxtamycin A/A′, along with two known analogues. These compounds are derived from the var and oxt gene clusters in Streptomyces varsoviensis/varR1, which primarily produce decaketide-derived tetracycline natural products, varsomycin A-B and oxytetracycline. Bioinformatic analysis combined with metabolite profiling of gene-disrupted mutants indicated that varsomycin C and C′ are co-produced by enzymes encoded in the var cluster, with contributions from oxtJ and oxtF in the oxt cluster, resulting in nonaketide-derived tricyclic scaffolds. Oxtamycin A and A′, along with the two analogues, are predicted to be biosynthesized by the oxt cluster. These results suggest that the minimal PKSs from both clusters possess intrinsic flexibility in controlling polyketide chain length, enabling the production of both decaketide and nonaketide intermediates, which represents a rare example of dual chain-length programming in type II PKSs. This flexibility reveals new natural sources of nonaketide biosynthetic enzymes and enriches the chemical diversity of tricyclic aromatic polyketides. Our findings deepen the understanding of type II PKS chain-length regulation and provide a foundation for future engineering of PKSs to produce customized bioactive aromatic polyketides. Full article
(This article belongs to the Special Issue Molecular Research on Microbial Natural Products)
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