7CP7

Crystal structure of FqzB, native proteins

7CP7 の概要

• エントリーDOI: 10.2210/pdb7cp7/pdb
• 分子名称: MAK1-like monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE, IODIDE ION, ... (4 entities in total)
• 機能のキーワード: monooxygenase (fad), oxidoreductase
• 由来する生物種: Aspergillus fumigatus Z5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52524.62

構造登録者

Hara, K.,Hashimoto, H.,Matsushita, T.,Kishimoto, S.,Watanabe, K. (登録日: 2020-08-06, 公開日: 2020-12-30, 最終更新日: 2023-11-29)

主引用文献

Matsushita, T.,Kishimoto, S.,Hara, K.,Hashimoto, H.,Watanabe, K.
Structural and Functional Analyses of a Spiro-Carbon-Forming, Highly Promiscuous Epoxidase from Fungal Natural Product Biosynthesis.
Biochemistry, 59:4787-4792, 2020

PubMed Abstract: Biosynthesis of fungal nonribosomal peptides frequently involves redox enzymes such as flavin-containing monooxygenase (FMO) to introduce complexity into the core chemical structure. One such example is the formation of spiro-carbons catalyzed by various oxidases. Because many chemically complex spiro-carbon-bearing natural products exhibit useful biological activities, understanding the mechanism of spiro-carbon biosynthesis is of great interest. We previously identified FqzB, an FMO from the fumiquinazoline biosynthetic pathway responsible for epoxidation of fumiquinazoline F that crosstalks with the fumitremorgin biosynthetic pathway to form spirotryprostatin A via epoxidation of the precursor fumitremorgin C. What makes FqzB more interesting is its relaxed substrate specificity, where it can accept a range of other substrates, including tryprostatins A and B along with its original substrate fumiquinazoline F. Here, we characterized FqzB crystallographically and examined FqzB and its site-specific mutants kinetically to understand how this promiscuous epoxidase works. Furthermore, the mutagenesis studies as well as computational docking experiments between the FqzB crystal structure and its known substrates spirotryprostatin A and B, as well as fumitremorgin C and fumiquinazoline F, provided insight into potential modes of substrate recognition and the source of broad substrate tolerance exhibited by this epoxidase. This study serves as a foundation for further characterization and engineering of this redox enzyme, which has potential utility as a valuable catalyst with broad substrate tolerance and an ability to introduce chemical complexity into carbon frameworks for chemoenzymatic and biosynthetic applications.

PubMed: 33332106
DOI: 10.1021/acs.biochem.0c00896

実験手法

X-RAY DIFFRACTION (2.4 Å)