9G64

F420-dependent oxidoreductase

9G64 の概要

• エントリーDOI: 10.2210/pdb9g64/pdb
• 分子名称: F420-dependent oxidoreductase (2 entities in total)
• 機能のキーワード: f420-dependent reductase, pepstatin biosynthesis, biosynthetic protein
• 由来する生物種: Streptomyces
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66321.45

構造登録者

Mueller, R.,Zhao, H.,Sikandar, A. (登録日: 2024-07-17, 公開日: 2025-06-11)

主引用文献

Mo, J.,Sikandar, A.,Zhao, H.,Bashiri, G.,Huo, L.,Empting, M.,Muller, R.,Fu, C.
Tandem ketone reduction in pepstatin biosynthesis reveals an F 420 H 2 -dependent statine pathway.
Nat Commun, 16:4531-4531, 2025

PubMed Abstract: Pepstatins are potent inhibitors of aspartic proteases, featuring two statine residues crucial for target binding. However, the biosynthesis of pepstatins, especially their statine substructure, remains elusive. Here, we discover and characterize an unconventional gene cluster responsible for pepstatin biosynthesis, comprising discrete nonribosomal peptide synthetase and polyketide synthase genes, highlighting its trans-acting and iterative nature. Central to this pathway is PepI, an FH-dependent oxidoreductase. The biochemical characterization of PepI reveals its role in the tandem reduction of β-keto pepstatin intermediates. PepI first catalyzes the formation of the central statine, then produces the C-terminal statine moiety. The post-assembly-line formation of statine by PepI contrasts with the previously hypothesized biosynthesis involving polyketide synthase ketoreductase domains. Structural studies, site-directed mutagenesis, and deuterium-labeled enzyme assays probe the mechanism of FH-dependent oxidoreductases and identify critical residues. Our findings uncover a unique statine biosynthetic pathway employing the only known iterative FH-dependent oxidoreductase to date.

PubMed: 40374670
DOI: 10.1038/s41467-025-59785-0

実験手法

X-RAY DIFFRACTION (1.65 Å)