8I4Z

CalA3 with hydrolysis product

Summary for 8I4Z

• Entry DOI: 10.2210/pdb8i4z/pdb
• EMDB information: 35189
• Descriptor: Beta-ketoacyl-acyl-carrier-protein synthase I, 11-oxidanylidene-11-(1~{H}-pyrrol-2-yl)undecanoic acid (2 entities in total)
• Functional Keywords: polyketide synthase, biosynthetic protein, transferase
• Biological source: Streptomyces chartreusis NRRL 3882
• Total number of polymer chains: 2
• Total formula weight: 357032.47

Authors

Wang, J.,Wang, Z. (deposition date: 2023-01-21, release date: 2023-02-22, Last modification date: 2024-07-03)

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 (3.97 Å)