Metabolically Engineered Escherichia coli for Efficient Conversion of Mixed Lignocellulosic Sugars into C3 Platform Chemicals

Abstract

The valorization of lignocellulosic hydrolysates, composed of mixed sugars, into industrial C3 platform chemicals remains a major challenge in the field of biorefinery due to carbon catabolite repression and inefficient sugar co-utilization. In this study, we constructed a robust Escherichia coli chassis that can spontaneously metabolize mixed sugars in lignocellulosic biomass by eliminating hierarchical substrate preference through metabolic rewiring. Using a synergistic strategy that combines adaptive evolution and pathway engineering, we enhanced assimilation of mixed sugars and metabolic flux toward a target hydroxy acid intermediate derived from malonyl-CoA. The engineered strain demonstrated significantly elevated titers from mixed sugars under fed-batch fermentation conditions. This work establishes a versatile microbial platform for the renewable synthesis of malonyl-CoA–derived C3 building blocks, offering a scalable and sustainable route to bio-based alternatives for conventional petrochemical intermediates.