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- Title
C–N bond formation by a polyketide synthase.
- Authors
Wang, Jialiang; Wang, Xiaojie; Li, Xixi; Kong, LiangLiang; Du, Zeqian; Li, Dandan; Gou, Lixia; Wu, Hao; Cao, Wei; Wang, Xiaozheng; Lin, Shuangjun; Shi, Ting; Deng, Zixin; Wang, Zhijun; Liang, Jingdan
- Abstract
Assembly-line polyketide synthases (PKSs) are molecular factories that produce diverse metabolites with wide-ranging biological activities. PKSs usually work by constructing and modifying the polyketide backbone successively. Here, we present the cryo-EM structure of CalA3, a chain release PKS module without an ACP domain, and its structures with amidation or hydrolysis products. The domain organization reveals a unique “∞”-shaped dimeric architecture with five connected domains. The catalytic region tightly contacts the structural region, resulting in two stabilized chambers with nearly perfect symmetry while the N-terminal docking domain is flexible. The structures of the ketosynthase (KS) domain illustrate how the conserved key residues that canonically catalyze C–C bond formation can be tweaked to mediate C–N bond formation, revealing the engineering adaptability of assembly-line polyketide synthases for the production of novel pharmaceutical agents.Polyketide synthases (PKSs) usually form C–C bonds in natural products biosynthesis. Here, the authors present cryo-EM structures of a PKS in complex with products, which provides insight into the mechanism of the unexpected C–N bond formation.
- Publication
Nature Communications, 2023, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-36989-w