Biomaterial Database

C-N bond formation by a polyketide synthase. 2023

Jialiang Wang, and Xiaojie Wang, and Xixi Li, and LiangLiang Kong, and Zeqian Du, and Dandan Li, and Lixia Gou, and Hao Wu, and Wei Cao, and Xiaozheng Wang, and Shuangjun Lin, and Ting Shi, and Zixin Deng, and Zhijun Wang, and Jingdan Liang

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

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.

UI	MeSH Term	Description	Entries
D048630	Polyketide Synthases	Large enzyme complexes composed of a number of component enzymes that are found in STREPTOMYCES which biosynthesize MACROLIDES and other polyketides.	Polyketide Synthase,6-Deoxyerythronolide-B Synthase,Epothilone Polyketide Synthase,Erythromycin Polyketide Synthase,Griseusin Polyketide Synthase,Niddamycin Polyketide Synthase,Polyketide Synthase L1,Polyketide Synthase WA,Rifamycin Polyketide Synthase,Sterigmatocystin Polyketide Synthase,Type I Polyketide Synthase,Type II Polyketide Beta-Ketoacyl Synthase,Urdamycin Polyketide Synthase,WdPKS1 Protein,WhiE Polyketide Synthase,6 Deoxyerythronolide B Synthase,Polyketide Synthase, Epothilone,Polyketide Synthase, Erythromycin,Polyketide Synthase, Griseusin,Polyketide Synthase, Niddamycin,Polyketide Synthase, Rifamycin,Polyketide Synthase, Sterigmatocystin,Polyketide Synthase, Urdamycin,Polyketide Synthase, WhiE,Protein, WdPKS1,Synthase L1, Polyketide,Synthase WA, Polyketide,Synthase, 6-Deoxyerythronolide-B,Synthase, Epothilone Polyketide,Synthase, Erythromycin Polyketide,Synthase, Griseusin Polyketide,Synthase, Niddamycin Polyketide,Synthase, Polyketide,Synthase, Rifamycin Polyketide,Synthase, Sterigmatocystin Polyketide,Synthase, Urdamycin Polyketide,Synthase, WhiE Polyketide,Synthases, Polyketide,Type II Polyketide Beta Ketoacyl Synthase
D020134	Catalytic Domain	The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.	Active Site,Catalytic Core,Catalytic Region,Catalytic Site,Catalytic Subunit,Reactive Site,Active Sites,Catalytic Cores,Catalytic Domains,Catalytic Regions,Catalytic Sites,Catalytic Subunits,Core, Catalytic,Cores, Catalytic,Domain, Catalytic,Domains, Catalytic,Reactive Sites,Region, Catalytic,Regions, Catalytic,Site, Active,Site, Catalytic,Site, Reactive,Sites, Active,Sites, Catalytic,Sites, Reactive,Subunit, Catalytic,Subunits, Catalytic