Unnatural lactam production by reprogrammed modular polyketide synthases in Pseudomonas putida

In recent years, type I polyketide synthases (PKSs) has emerged as an enticing platform for the production of novel molecules by reconstituting their modules, expanding the chemical landscape beyond the limitations of conventional metabolic engineering. This study reports a retrobiosynthesis approach to produce five-carbon lactam and its derivatives through the heterologous expression of reprogrammed PKS within Pseudomonas putida KT2440, a widely employed organism for the sustainable commodity chemical production. Combining with host optimization to prevent the catabolism of target product and engineering to facilitate the production of unique acyl-CoA extender units for PKS, this strategy enables mg · l−1 scale microbial production of unnatural lactams, even utilizing plant biomass hydrolysate as a starting material. The resulting novel nylons, derived from the polymerization of these unexplored monomers, hold promise for advancing textile materials, providing sustainable alternatives with potential across various industrial applications.