2. Assembly Line Biosynthesis and Bioengineering
Assembly line enzymes are the most sophisticated biosynthetic machinery that produce numerous structural varieties. Among these products, polyketides and nonribosomal peptides are the leading class of natural products in antibiotics discovery and development. The biosynthesis of polyketides, for example in macrolide antibiotics erythromycin, is catalyzed by a set of multimodular polyketide synthase (PKS) megaenzymes in a sequential manner. This assembly line biosynthesis has been a target for rational bioengineering since their discovery in 1990s, though we are still far from flexible reprogramming of these assembly line enzymes. Interestingly, the exponentially accumulating sequences of biosynthetic genes now offers opportunity to understand the evolution of multimodular PKSs and NRPSs in nature. Our group aims to understand the evolution of polyketide and nonribosomal peptide biosynthesis and apply it for evolution-guided engineering to realize plug-and-play reprogramming of assembly line biosynthesis.