8AHZ

Native VirD of Streptomyces virginiae

8AHZ の概要

• エントリーDOI: 10.2210/pdb8ahz/pdb
• 関連するPDBエントリー: 8AHQ
• 分子名称: Enoyl-CoA hydratase, 1,2-ETHANEDIOL, IMIDAZOLE, ... (5 entities in total)
• 機能のキーワード: enoyl-coa hydratase, beta-methylation, antibiotic, acp, polyketide, pks, biosynthetic protein
• 由来する生物種: Streptomyces virginiae
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 81480.38

構造登録者

Collin, S.,Gruez, A. (登録日: 2022-07-25, 公開日: 2023-03-15, 最終更新日: 2024-10-09)

主引用文献

Collin, S.,Cox, R.J.,Paris, C.,Jacob, C.,Chagot, B.,Weissman, K.J.,Gruez, A.
Decrypting the programming of beta-methylation in virginiamycin M biosynthesis.
Nat Commun, 14:1327-1327, 2023

PubMed Abstract: During biosynthesis by multi-modular trans-AT polyketide synthases, polyketide structural space can be expanded by conversion of initially-formed electrophilic β-ketones into β-alkyl groups. These multi-step transformations are catalysed by 3-hydroxy-3-methylgluratryl synthase cassettes of enzymes. While mechanistic aspects of these reactions have been delineated, little information is available concerning how the cassettes select the specific polyketide intermediate(s) to target. Here we use integrative structural biology to identify the basis for substrate choice in module 5 of the virginiamycin M trans-AT polyketide synthase. Additionally, we show in vitro that module 7, at minimum, is a potential additional site for β-methylation. Indeed, analysis by HPLC-MS coupled with isotopic labelling and pathway inactivation identifies a metabolite bearing a second β-methyl at the expected position. Collectively, our results demonstrate that several control mechanisms acting in concert underpin β-branching programming. Furthermore, variations in this control - whether natural or by design - open up avenues for diversifying polyketide structures towards high-value derivatives.

PubMed: 36899003
DOI: 10.1038/s41467-023-36974-3

実験手法

X-RAY DIFFRACTION (1.7 Å)