8XJU

Cryo-EM structure of colibactin assembly line polyketide synthase ClbI (apo state)

8XJU の概要

• エントリーDOI: 10.2210/pdb8xju/pdb
• EMDBエントリー: 38406
• 分子名称: Polyketide synthase (1 entity in total)
• 機能のキーワード: colibactin, microbiome, polyketide synthase, colorectal cancer, nrps-pks hybrid, biosynthetic protein, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 221305.48

構造登録者

Kim, M.,Kim, J.,Kang, J.Y. (登録日: 2023-12-22, 公開日: 2025-05-21, 最終更新日: 2025-07-16)

主引用文献

Kim, M.,Kim, J.,Lee, G.S.,Olinares, P.D.B.,Airan, Y.,Chow, J.L.,Park, J.,Jeong, Y.,Park, J.,Chait, B.T.,Herzon, S.B.,Kim, C.S.,Kang, J.Y.
Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin.
Structure, 33:1208-1223.e5, 2025

PubMed Abstract: Colibactin, a human microbiome-derived genotoxin, promotes colorectal cancer by damaging the host gut epithelial genomes. While colibactin is synthesized via a hybrid non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway, known as pks or clb, the structural details of its biosynthetic enzymes remain limited, hindering our understanding of its biosynthesis and clinical application. In this study, we report the cryo-EM structures of two colibactin-producing PKS enzymes, ClbC and ClbI, captured in different reaction states using a substrate-mimic crosslinker. Our structural analysis revealed the binding sites of carrier protein (CP) domains of the ClbC and ClbI on their ketosynthase (KS) domains. Further, we identified a novel NRPS-PKS docking interaction between ClbI and its upstream enzyme, ClbH, mediated by the C-terminal peptide ClbH and the dimeric interface of ClbI, establishing a 1:2 stoichiometry. These findings advance our understanding of colibactin assembly line and provide broader insights into NRPS-PKS natural product biosynthesis mechanisms.

PubMed: 40381618
DOI: 10.1016/j.str.2025.04.017

実験手法

ELECTRON MICROSCOPY (2.91 Å)