6LE0

A nonspecific heme-binding cyclase catalyzes [4 + 2] cycloaddition during neoabyssomicin biosynthesis

6LE0 の概要

• エントリーDOI: 10.2210/pdb6le0/pdb
• 分子名称: AbmU (2 entities in total)
• 機能のキーワード: cyclase, biosynthetic protein
• 由来する生物種: Streptomyces koyangensis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95571.46

構造登録者

Ju, J.J. (登録日: 2019-11-23, 公開日: 2020-11-25, 最終更新日: 2024-10-16)

主引用文献

Li, Q.,Ding, W.,Tu, J.,Chi, C.,Huang, H.,Ji, X.,Yao, Z.,Ma, M.,Ju, J.
Nonspecific Heme-Binding Cyclase, AbmU, Catalyzes [4 + 2] Cycloaddition during Neoabyssomicin Biosynthesis.
Acs Omega, 5:20548-20557, 2020

PubMed Abstract: Diels-Alder (DA) [4 + 2]-cycloaddition reactions rank among the most powerful transformations in synthetic organic chemistry; biosynthetic examples, however, are few and far between. We report here a heme-binding cyclase, AbmU, that catalyzes an essential [4 + 2] cycloaddition during neoabyssomicin scaffold assembly. In vivo genetic and in vitro biochemical analyses strongly suggest that AbmU catalyzes an intramolecular and stereoselective [4 + 2] cycloaddition to form a spirotetronate skeleton from an acyclic substrate featuring both a terminal 1,3-diene and an exo-methylene group. Biochemical assays and X-ray diffraction analyses reveal that AbmU binds nonspecifically to a heme cofactor and that this association does not play a catalytic role in AbmU catalysis. A detailed study of the AbmU crystal structure reveals a unique mode of substrate binding and reaction catalysis; His160 forms a H-bond with the C-1 carbonyl O-atom of the acyclic substrate, and the imidazole of the same amino acid directs the tetronate moiety of acyclic substrate toward the terminal Δ, Δ-diene moiety, thereby facilitating intramolecular DA chemistry. Our findings expand upon what is known about mechanistic diversities available to biosynthetic [4 + 2] cyclases and help to lay the foundation for the use of AbmU in possible industrial applications.

PubMed: 32832808
DOI: 10.1021/acsomega.0c02776

実験手法

X-RAY DIFFRACTION (2.51 Å)