Harnessing microbial co-culture to increase the production of known secondary metabolites

Yu Zhen Li, Wan Qi Zhang, Peng Fei Hu, Qiong Qiong Yang, István Molnár*, Peng Xu*, Bo Bo Zhang*

*Corresponding author for this work

Research output: Contribution to journalReview Articlepeer-review

Abstract

Secondary metabolites (SMs) are naturally occurring defense or signaling molecules that are also utilized as human and animal drugs, crop protection agents, and fine chemicals. Currently, SMs are primarily produced in monoculture settings, devoid of the intricate microbial interactions found in natural environments. Monoculture may lead to the silencing of gene clusters, requiring various genetic or bioprocess strategies to activate the biosynthesis of the corresponding metabolites. Less considered is the effect of monoculture on the efficiency of the production of important, known SMs during microbial fermentations. Co-culturing aims to mimic the complexity of natural microbial habitats, thus may increase the titer, the rate and/or the yield of fermentations. This review summarizes the progress in utilizing co-culture to promote the synthesis of known SMs by describing the types of various microbial co-cultures, listing the mechanisms for enhancing the biosynthesis of SMs, and navigating the challenges and strategies for applying such an approach in the biotechnology industries.

Original languageEnglish
Pages (from-to)623-637
JournalNatural Product Reports
Volume42
DOIs
Publication statusPublished - 2025
MoE publication typeA2 Review article in a scientific journal

Funding

This work was supported by the National Natural Science Foundation of China (32472313 and 32072184 to B. B. Z.), the Natural Science Foundation of Guangdong Province (2023A1515011798 to B. B. Z.), the Research Start-up Foundation of Shantou University (NTF20003 to B. B. Z., NTF22003 to Q. Q. Y.), and VTT Technical Research Centre of Finland (to I. M.).

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