9JEM

Co-crystal structure of PHBDD-L163G with product N-isopropyl-4-methylbenzamide

これはPDB形式変換不可エントリーです。

9JEM の概要

• エントリーDOI: 10.2210/pdb9jem/pdb
• 分子名称: 4-hydroxybenzaldehyde dehydrogenase (NADP(+)), 4-methyl-~{N}-propan-2-yl-benzamide (3 entities in total)
• 機能のキーワード: oxidative amidase, aldehyde dehydrogenase, amide bond, nadp+-dependent, oxidoreductase
• 由来する生物種: Pseudomonas putida (Arthrobacter siderocapsulatus)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 213757.16

構造登録者

Yang, J.,Qiu, X.,Gao, L. (登録日: 2024-09-03, 公開日: 2026-01-14, 最終更新日: 2026-03-04)

主引用文献

Gao, L.,Qiu, X.,Yang, J.,Hu, K.,Li, P.,Li, W.,Gao, F.,Gallou, F.,Kleinbeck, F.,Lei, X.
Engineered aldehyde dehydrogenases for amide bond formation.
Science, 391:eadw3365-eadw3365, 2026

PubMed Abstract: Amide bond formation is widely used in pharmaceutical synthesis, typically involving stoichiometric coupling reagents to activate carboxylic acid substrates for a condensation reaction. As an alternative approach, we repurposed aldehyde dehydrogenases into oxidative amidases by creating a more hydrophobic and spacious catalytic pocket for amines to capture the thioester intermediate. This biocatalyst efficiently facilitates the formation of amide bonds between diverse aldehydes and amines. We also developed a two-step enzymatic cascade to synthesize amides from broadly available aliphatic alcohols. This biocatalytic strategy enabled the redesign of synthetic routes for five drug molecules. Our findings highlight the potential of oxidative amidases in advancing the synthesis of structurally diverse drug molecules through efficient amide bond formation.

PubMed: 41610224
DOI: 10.1126/science.adw3365

実験手法

X-RAY DIFFRACTION (1.83 Å)