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TitleC-N bond formation by a polyketide synthase.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1319, Year 2023
Publish dateMar 10, 2023
AuthorsJialiang Wang / Xiaojie Wang / Xixi Li / LiangLiang Kong / Zeqian Du / Dandan Li / Lixia Gou / Hao Wu / Wei Cao / Xiaozheng Wang / Shuangjun Lin / Ting Shi / Zixin Deng / Zhijun Wang / Jingdan Liang /
PubMed AbstractAssembly-line polyketide synthases (PKSs) are molecular factories that produce diverse metabolites with wide-ranging biological activities. PKSs usually work by constructing and modifying the ...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.
External linksNat Commun / PubMed:36899013 / PubMed Central
MethodsEM (single particle)
Resolution3.38 - 4.55 Å
Structure data

EMDB-32863, PDB-7wvz:
CalA3_modular PKS_KS-AT-DH-KR
Method: EM (single particle) / Resolution: 3.38 Å

EMDB-32864: Structure of an assembly-line polyketide synthase module with typical docking domain position
Method: EM (single particle) / Resolution: 4.55 Å

EMDB-35188, PDB-8i4y:
CalA3 complex structure with amidation product
Method: EM (single particle) / Resolution: 3.84 Å

EMDB-35189, PDB-8i4z:
CalA3 with hydrolysis product
Method: EM (single particle) / Resolution: 3.97 Å

Chemicals

ChemComp-ONF:
11-oxidanylidene-11-(1~{H}-pyrrol-2-yl)undecanoic acid

ChemComp-3HA:
3-HYDROXYANTHRANILIC ACID / 3-Hydroxyanthranilic acid

Source
  • Streptomyces chartreusis NRRL 3882cha (bacteria)
  • streptomyces chartreusis nrrl 3882 (bacteria)
KeywordsTRANSFERASE / megaenzyme / HYDROLASE / polyketide synthase / BIOSYNTHETIC PROTEIN

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