9UDE

Crystal structure of MonCI in complex with diepoxidized farnesyl acetate

9UDE の概要

• エントリーDOI: 10.2210/pdb9ude/pdb
• 分子名称: MonCI, FLAVIN-ADENINE DINUCLEOTIDE, diepoxidized farnesyl acetate, ... (6 entities in total)
• 機能のキーワード: fad dependent monooxygenase, epoxidase, mutant, flavoprotein
• 由来する生物種: Streptomyces virginiae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112225.36

構造登録者

Xiao, H.L.,Guan, Y.Z.,Chen, X. (登録日: 2025-04-06, 公開日: 2025-04-16, 最終更新日: 2025-05-21)

主引用文献

Deng, Y.,Guan, Y.,Xiao, H.,Kang, Y.,Dang, D.,Jiang, G.,Wang, Q.,Yang, Y.,Cheng, L.,Zang, Y.,Zhang, S.,He, W.,Hotta, K.,Liu, J.Q.,Yang, Z.,Chen, X.
Mechanistic and molecular insights into iterative triepoxidation catalyzed by monooxygenase MonCI using a natural substrate analog.
Int.J.Biol.Macromol., 311:142876-142876, 2025

PubMed Abstract: Monensin, a polyether antibiotic produced by Streptomyces cinnamonensis, is synthesized through a series of stereospecific epoxidations orchestrated by the FAD-dependent monooxygenase MonCI. This study presents the crystal structure of MonCI in complex with a substrate analog, farnesyl acetate, which undergoes in vitro epoxidation at all three olefinic sites by MonCI. Additionally, we have solved the crystal structures of MonCI in complex with mono- and bis-epoxide intermediates. Structural analysis revealed that the interactions between MonCI and its substrate are predominantly hydrophobic, with residue Y208 playing a crucial role in substrate translocation. Computational modeling emphasizes the importance of FAD proximity to each olefinic group for efficient catalysis, providing insight into the mechanistic pathways for the first, second, and third epoxidations. Notably, when combined with electrochemical techniques, the yield of tri-epoxide farnesyl acetate reached 94 %, surpassing traditional enzymatic catalysis. This work not only elucidates the catalytic mechanism of MonCI but also underscores its potential as an effective biocatalyst for processive epoxidation in organic synthesis.

PubMed: 40203940
DOI: 10.1016/j.ijbiomac.2025.142876

実験手法

X-RAY DIFFRACTION (2.65 Å)