Metabolic Engineering of Escherichia coli for Efficient 3-Hydroxypropionic Acid Production from Mixed Sugars via Malonyl-CoA Enhancement

Abstract

The sustainable biosynthesis of industrially relevant chemicals from lignocellulosic biomass presents a viable alternative to fossil fuel–based production methods. However, efficient microbial conversion of key lignocellulosic sugars such as glucose and xylose remain a major challenge due to carbon catabolite repression and suboptimal xylose metabolism in commonly used host strains like Escherichia coli. In this study, we developed an E. coli strain capable of efficiently converting mixed sugars into 3-hydroxypropionic acid (3-HP), an important platform chemical. Adaptive laboratory evolution was employed to enhance the strain’s growth on xylose, followed by targeted genetic modifications to facilitate simultaneous utilization of glucose and xylose. These modifications led to an elevated intracellular malonyl-CoA pool, a crucial intermediate in the 3-HP biosynthetic pathway. Our findings highlight a promising strategy for producing malonyl-CoA-derived biochemicals from renewable biomass sources.