4Y1B

Structure of crotonyl-CoA carboxylase/reductase AntE V350A in complex with NADP

4Y1B の概要

• エントリーDOI: 10.2210/pdb4y1b/pdb
• 関連するPDBエントリー: 4Y0K
• 分子名称: AntE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: oxidoreductase, transferase, carboxylase, antimycin biosynthesis
• 由来する生物種: Streptomyces sp. NRRL 2288
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47353.96

構造登録者

Abe, I.,Zhang, L.,Mori, T. (登録日: 2015-02-07, 公開日: 2015-09-23, 最終更新日: 2023-11-08)

主引用文献

Zhang, L.,Mori, T.,Zheng, Q.,Awakawa, T.,Yan, Y.,Liu, W.,Abe, I.
Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis
Angew.Chem.Int.Ed.Engl., 54:13462-13465, 2015

PubMed Abstract: Bioengineering of natural product biosynthesis is a powerful approach to expand the structural diversity of bioactive molecules. However, in polyketide biosynthesis, the modification of polyketide extender units, which form the carbon skeletons, has remained challenging. Herein, we report the rational control of polyketide extender units by the structure-based engineering of a crotonyl-CoA carboxylase/reductase (CCR), in the biosynthesis of antimycin. Site-directed mutagenesis of the CCR enzyme AntE, guided by the crystal structure solved at 1.5 Å resolution, expanded its substrate scope to afford indolylmethylmalonyl-CoA by the V350G mutation. The mutant A182L selectively catalyzed carboxylation over the regular reduction. Furthermore, the combinatorial biosynthesis of heterocycle- and substituted arene-bearing antimycins was achieved by an engineered Streptomyces strain bearing AntE(V350G). These findings deepen our understanding of the molecular mechanisms of the CCRs, which will serve as versatile biocatalysts for the manipulation of building blocks, and set the stage for the rational design of polyketide biosynthesis.

PubMed: 26356484
DOI: 10.1002/anie.201506899

実験手法

X-RAY DIFFRACTION (1.5 Å)