Ring formation is a common strategy to diversify natural products, and the molecular basis of cyclization specificity is a vigorously pursued topic in natural product biosynthesis. Polyketides are a class of natural products with highly diverse chemical structures and pharmaceutical activities. How the polyketide synthase (PKS) promotes highly specific cyclization is not well understood. Herein we present the crystal structures of PKS domains that promote different cyclization patterns. The critical comparison allows a rationale behind the vast cyclization diversity observed in polyketide natural products.

Molecular origami in nature: Chemical biology of polyketide cyclization

243rd National Meeting (2012)

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