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Title | C-N bond formation by a polyketide synthase. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 1319, Year 2023 |
Publish date | Mar 10, 2023 |
Authors | Jialiang 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 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 ...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 links | Nat Commun / PubMed:36899013 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.38 - 4.55 Å |
Structure data | EMDB-32863, PDB-7wvz: EMDB-32864: Structure of an assembly-line polyketide synthase module with typical docking domain position EMDB-35188, PDB-8i4y: EMDB-35189, PDB-8i4z: |
Chemicals | ChemComp-ONF: ChemComp-3HA: |
Source |
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Keywords | TRANSFERASE / megaenzyme / HYDROLASE / polyketide synthase / BIOSYNTHETIC PROTEIN |