Decoding microbial interactions: Interaction networks and regulatory strategies for medium-chain fatty acid...

The anaerobic biosynthesis of medium-chain fatty acids (MCFAs) as valorized bio-based chemicals relies on intricate and dynamic interaction networks within microbial communities. This review systematically summarizes the key mechanisms and regulatory strategies driving MCFA biosynthesis in terms of microbial interactions, with a focus on electron donor-acceptor generation and chain elongation (CE) processes. The functional stability and resilience of anaerobic fermentation systems are collectively sustained by microbial diversity via modular functional partitioning, metabolic complementarity, resilience against perturbations, and environmental adaptation. Notably, substrate competition and syntrophic symbiosis between functional taxa directly govern the directionality and efficiency of the metabolic flux. Carbon source preferences and environmental factors synergistically steer pathway selection, while exogenous interventions such as enhanced electron transfer or niche occupation optimize microbial cooperation. In addition, quorum sensing and electrochemical synergy further balance inter-species competition to achieve a dynamic equilibrium between metabolic branch inhibition and enrichment of CE consortia. These multidimensional interaction mechanisms provide high-purity electron donors and stable metabolic foundations for MCFA synthesis to guide directional microbial engineering strategies to enhance product yields. This study systematically summarized how microbial interaction networks drive efficient MCFA biosynthesis via a multi-scale coordination between various mechanisms, including metabolic flux partitioning control, environmental response feedback, and functional modularization design, providing a theoretical foundation for resolving critical challenges during anaerobic MCFA fermentation.