Engineering fatty acid synthases for directed polyketide production

In vitro and in silico analysis enables the rational design of fatty acid synthase (FAS)-mediated pathways for the compartmentalized production of desirable fatty acids and a polyketide lactone. In this study, we engineered fatty acid synthases (FAS) for the biosynthesis of short-chain fatty acids and polyketides, guided by a combined in vitro and in silico approach. Along with exploring the synthetic capability of FAS, we aim to build a foundation for efficient protein engineering, with the specific goal of harnessing evolutionarily related megadalton-scale polyketide synthases (PKS) for the tailored production of bioactive natural compounds.