[ASAP] Engineered Modular Polyketide Synthases Elucidate How Enoylreductases Collaborate with Downstream Acyl Carrier Proteins and Ketosynthases to Set Stereocenters

AI Insight

This study uses engineered modular polyketide synthases (PKSs) to investigate the mechanistic basis by which enoylreductase (ER) domains establish stereocenters during polyketide biosynthesis. The researchers demonstrate that ER domains do not act in isolation but collaborate functionally with downstream acyl carrier proteins (ACPs) and ketosynthases (KSs) to control the stereochemical outcome of the reduction reaction. By constructing chimeric PKS modules with systematically varied domain compositions, the work clarifies how protein-protein interactions and substrate recognition across multiple domains collectively determine the configuration of methyl-bearing stereocenters in polyketide natural products.

Why it matters

Understanding the stereochemical logic of PKS machinery is critical for rational bioengineering of these assembly lines to produce novel polyketide-derived pharmaceuticals, including antibiotics and anticancer agents, with defined and therapeutically relevant stereochemistry.