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

Covering: 2019 to 2024Secondary 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.