Biosynthetic Pathways and Regulation of Antibacterial Compounds From Endophytic Fungi: From Chemistry to Genomics and Biotechnology.
6 affiliations
- 1Institute For Advanced Studies, New Uzbekistan University, Tashkent, Uzbekistan.
- 2Department of Chemistry, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, Tanjong Malim, Perak, Malaysia.
- 3Department of Pure and Industrial Chemistry, Faculty of Natural and Applied Sciences, Umaru Musa Yar'adua University, Katsina, Nigeria.
- 4Faculty of Chemistry and Biology, Karshi State University, Karshi, Uzbekistan.
- 5Division of Life Science and Center for Chinese Medicine R&D, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
- 6S.Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, Tashkent, Uzbekistan.
Abstract
Endophytic fungi are non-pathogenic symbionts that represent a rich source of structurally diverse bioactive secondary metabolites. However, genome-mining studies reveal that most of their biosynthetic gene clusters (BGCs) remain transcriptionally silent under standard laboratory conditions, leaving much of their chemical diversity unexplored. This review examines antibacterial natural products from endophytic fungi by integrating three complementary aspects: metabolite chemistry, biosynthetic pathways, and strategies for activating cryptic BGCs. Endophytic fungi produce polyketides, non-ribosomal peptides, terpenoids, phenylpropanoid-derived compounds, and hybrid metabolites with antibacterial activities mediated through inhibition of ribosomes, cell wall and membrane biosynthesis, and bacterial resistance mechanisms. Their genomes encode diverse PKS, NRPS, TPS, and hybrid biosynthetic systems, many of which remain cryptic. Advances in chemical elicitation, co-cultivation, epigenetic modulation, CRISPR-based engineering, genome mining, and machine learning are accelerating the activation of silent clusters and the assignment of BGCs to their metabolites. Several fungal metabolites exhibit potent activity against multidrug-resistant pathogens, including MRSA, and some enhance the efficacy of existing antibiotics. This review highlights current progress, identifies remaining challenges in metabolite production and BGC annotation, and outlines future directions for translating endophytic fungi into a sustainable platform for next-generation antibacterial drug discovery.
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BibTeX
@article{eshboev2026biosynthetic,
title = {{Biosynthetic Pathways and Regulation of Antibacterial Compounds From Endophytic Fungi: From Chemistry to Genomics and Biotechnology.}},
author = {Farkhod Eshboev and Abubakar Siddiq Salihu and Lobar Khayrullaeva and Doniyor Khamdamov and Alex X Gao and Kamila Mardieva and Wan Mohd Nuzul Hakimi Wan Salleh and Shakhnoz Azimova and Karl W K Tsim},
journal = {Chemistry \& biodiversity},
year = {2026},
month = oct,
doi = {10.1002/cbdv.71888},
url = {https://europepmc.org/article/MED/42960687},
note = {CC BY},
}
RIS
TY - JOUR
TI - Biosynthetic Pathways and Regulation of Antibacterial Compounds From Endophytic Fungi: From Chemistry to Genomics and Biotechnology.
AU - Farkhod Eshboev
AU - Abubakar Siddiq Salihu
AU - Lobar Khayrullaeva
AU - Doniyor Khamdamov
AU - Alex X Gao
AU - Kamila Mardieva
AU - Wan Mohd Nuzul Hakimi Wan Salleh
AU - Shakhnoz Azimova
AU - Karl W K Tsim
PY - 2026
DA - 2026/10/30
JO - Chemistry & biodiversity
DO - 10.1002/cbdv.71888
UR - https://europepmc.org/article/MED/42960687
AB - Endophytic fungi are non-pathogenic symbionts that represent a rich source of structurally diverse bioactive secondary metabolites. However, genome-mining studies reveal that most of their biosynthetic gene clusters (BGCs) remain transcriptionally silent under standard laboratory conditions, leaving much of their chemical diversity unexplored. This review examines antibacterial natural products from endophytic fungi by integrating three complementary aspects: metabolite chemistry, biosynthetic pathways, and strategies for activating cryptic BGCs. Endophytic fungi produce polyketides, non-ribosomal peptides, terpenoids, phenylpropanoid-derived compounds, and hybrid metabolites with antibacterial activities mediated through inhibition of ribosomes, cell wall and membrane biosynthesis, and bacterial resistance mechanisms. Their genomes encode diverse PKS, NRPS, TPS, and hybrid biosynthetic systems, many of which remain cryptic. Advances in chemical elicitation, co-cultivation, epigenetic modulation, CRISPR-based engineering, genome mining, and machine learning are accelerating the activation of silent clusters and the assignment of BGCs to their metabolites. Several fungal metabolites exhibit potent activity against multidrug-resistant pathogens, including MRSA, and some enhance the efficacy of existing antibiotics. This review highlights current progress, identifies remaining challenges in metabolite production and BGC annotation, and outlines future directions for translating endophytic fungi into a sustainable platform for next-generation antibacterial drug discovery.
SN - 1612-1872
SN - 1612-1880
ER -