7WVZ

CalA3_modular PKS_KS-AT-DH-KR

Summary for 7WVZ

• Entry DOI: 10.2210/pdb7wvz/pdb
• EMDB information: 32863
• Descriptor: Beta-ketoacyl-acyl-carrier-protein synthase I (1 entity in total)
• Functional Keywords: megaenzyme, hydrolase, transferase
• Biological source: Streptomyces chartreusis NRRL 3882
• Total number of polymer chains: 2
• Total formula weight: 361053.91

Authors

Wang, J.,Wang, Z. (deposition date: 2022-02-12, release date: 2023-02-22, Last modification date: 2023-10-11)

Primary citation

Wang, J.,Wang, X.,Li, X.,Kong, L.,Du, Z.,Li, D.,Gou, L.,Wu, H.,Cao, W.,Wang, X.,Lin, S.,Shi, T.,Deng, Z.,Wang, Z.,Liang, J.
C-N bond formation by a polyketide synthase.
Nat Commun, 14:1319-1319, 2023

PubMed 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.

PubMed: 36899013
DOI: 10.1038/s41467-023-36989-w

Experimental method

ELECTRON MICROSCOPY (3.38 Å)