7FE5

AvmM Catalyzes Macrocyclization in Alchivemycin A Biosynthesis

7FE5 の概要

• エントリーDOI: 10.2210/pdb7fe5/pdb
• 関連するPDBエントリー: 7FE0
• 分子名称: AvmM, CACODYLATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: alchivemycin, biosynthetic protein, michael addition, macrocyclization
• 由来する生物種: Streptomyces sp. NBRC 109436
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71787.45

構造登録者

Zhang, B.,Ge, H.M. (登録日: 2021-07-19, 公開日: 2021-09-01, 最終更新日: 2023-11-29)

主引用文献

Zhu, H.J.,Zhang, B.,Wei, W.,Liu, S.H.,Xiang, L.,Zhu, J.,Jiao, R.H.,Igarashi, Y.,Bashiri, G.,Liang, Y.,Tan, R.X.,Ge, H.M.
AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis.
Nat Commun, 13:4499-4499, 2022

PubMed Abstract: Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1). We show through in vivo gene deletion, in vitro biochemical assay and isotope labelling experiments that AvmM catalyzes tandem dehydration and Michael-type addition to generate the core scaffold of 1. Mechanistic studies by crystallography, DFT calculations and MD simulations of AvmM reveal that the reactions are achieved with assistance from the special tenuazonic acid like moiety of substrate. Our results thus uncover an uncharacterized macrocyclization strategy in natural product biosynthesis.

PubMed: 35922406
DOI: 10.1038/s41467-022-32088-4

実験手法

X-RAY DIFFRACTION (2.09 Å)