9VBT

Cryo-EM structure of the multi-component acyltransferase complex MucABC from Streptococcus macacae at a stoichiometric ratio of 4:4:4

これはPDB形式変換不可エントリーです。

9VBT の概要

• エントリーDOI: 10.2210/pdb9vbt/pdb
• EMDBエントリー: 64933
• 分子名称: 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III, C-terminal domain protein, 2,4-diacetylphloroglucinol biosynthesis protein PhlB family protein, 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III domain protein, ... (4 entities in total)
• 機能のキーワード: enzyme complex, thiolase, friedel-crafts acylation, biosynthesis, transferase
• 由来する生物種: Streptococcus macacae NCTC 11558; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 406001.54

構造登録者

Luo, Z.,Shen, Z.,Liao, G.,Tang, X.,Pan, X. (登録日: 2025-06-04, 公開日: 2026-02-11, 最終更新日: 2026-03-18)

主引用文献

Liao, G.,Sun, R.,Shen, Z.,Luo, Z.,Pang, C.,Shen, Z.,Wei, A.,Mi, C.,Wu, G.,Li, F.,Li, Y.X.,Hoi, K.K.,Pan, X.,Tang, X.
Evolutionary repurposing of a metabolic thiolase complex enables antibiotic biosynthesis.
Nat Commun, 17:-, 2026

PubMed Abstract: The functional diversification of biosynthetic enzymes underlies the chemical richness of natural products, yet how primary metabolic enzymes evolve to acquire specialized functions in secondary metabolism remains elusive. Here, we report a tripartite enzyme complex from oral Streptococcus species-comprising 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS), acetyl-CoA acetyltransferase (ACAT), and a DUF35 protein-that catalyzes an unusual Friedel-Crafts C-acetylation on a pyrrolidine-2,4-dione scaffold, completing the biosynthesis of the antibiotic reutericyclin A. Cryo-electron microscopy of the S. macacae-derived thiolase complex (SmaATase) reveals a conserved architecture resembling the archaeal HMGS/ACAT/DUF35 complex involved in the mevalonate pathway, yet with key catalytic residues rewired to reprogram substrate specificity. Biochemical characterization, molecular modeling, and evolutionary analysis confirmed that the ancestral activity of HMG-CoA synthesis has been lost, while the complex has been repurposed to mediate Friedel-Crafts C-acylation of small molecule acceptors. These findings reveal a rare example of thiolase complex neofunctionalization, shedding light on an underexplored trajectory in enzyme evolution and offering a template for engineering C-C bond-forming catalysts in synthetic biology.

PubMed: 41617701
DOI: 10.1038/s41467-026-68910-6

実験手法

ELECTRON MICROSCOPY (2.32 Å)