Multiplex metabolic engineering for enhanced indole-3-acetic acid production via optimized biosynthetic pathways in E. coli

Abstract

IAA is a key auxin that regulates plant growth and development. Engineering E. coli as a microbial cell factory provides a sustainable alternative to petrochemical-based production methods by using glucose as a feedstock. This review outlines fundamental strategies that enhance microbial IAA synthesis while simplifying technical concepts for broader understanding. Key approaches include overexpressing genes in the shikimate pathway and modifying central carbon metabolism (PP and EMP pathways) to increase precursor availability, particularly E4P and PEP. Enhancing cofactor supply, through improved NAD(P)H and ATP regeneration and FMN and FAD preservation, supports the energy and redox demands of IAA biosynthesis. Enhancing intracellular L-tryptophan levels by boosting import and limiting efflux further contributes to IAA productivity. Balancing growth with metabolite output ensures process efficiency. The review highlights forward-looking strategies, including machine learning for pathway design, genome-scale modeling to identify bottlenecks, and the use of modular or co-culture engineering to optimize microbial IAA biosynthesis. It underscores the potential of engineered E. coli as a sustainable platform for IAA production, paving the way for greener agricultural practices and reduced reliance on petrochemicals.