PNNL

Abstract

In recent years, polyketide synthases (PKSs) have emerged as an enticing biocatalyst for the production of new-to-nature molecules, expanding the chemical landscape beyond the limitations of conventional metabolic engineering. This study introduces a PKS-based retrobiosynthesis approach to produce unnatural lactams using the microbial host Pseudomonas putida, a microorganism widely explored for the sustainable production of commodity chemicals. Rational host engineering coupled with the heterologous expression of a reprogrammed PKS enabled the production of d-valerolactam (VL) and three enantiopure a-substituted analogs from renewable carbon sources. Converting these a-substituted VLs into their corresponding N-acryloyl derivatives and employing RAFT polymerization resulted in a new class of bio-derived polymers with potential uses in biomedical applications. Overall, these interdisciplinary efforts showcase the effectiveness and versatility of a PKS-based retrobiosynthesis approach for the exploration of novel biomaterials.