8F91

OxyB, a cytochrome P450 involved in keratinimicin biosynthesis

8F91 の概要

• エントリーDOI: 10.2210/pdb8f91/pdb
• 分子名称: OxyB, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: cytochrome p450, monooxygenase, keratinimicin, oxidoreductase
• 由来する生物種: Amycolatopsis keratiniphila
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47042.20

構造登録者

Ireland, K.A.,Davis, K.M. (登録日: 2022-11-22, 公開日: 2023-07-19, 最終更新日: 2024-10-23)

主引用文献

Hauser, N.,Ireland, K.A.,Chioti, V.T.,Forneris, C.C.,Davis, K.M.,Seyedsayamdost, M.R.
Robust Chemoenzymatic Synthesis of Keratinimicin Aglycone Analogues Facilitated by the Structure and Selectivity of OxyB.
Acs Chem.Biol., 18:1473-1479, 2023

PubMed Abstract: The emergence of multidrug-resistant pathogens poses a threat to public health and requires new antimicrobial agents. As the archetypal glycopeptide antibiotic (GPA) used against drug-resistant Gram-positive pathogens, vancomycin provides a promising starting point. Peripheral alterations to the vancomycin scaffold have enabled the development of new GPAs. However, modifying the core remains challenging due to the size and complexity of this compound family. The recent successful chemoenzymatic synthesis of vancomycin suggests that such an approach can be broadly applied. Herein, we describe the expansion of chemoenzymatic strategies to encompass type II GPAs bearing all aromatic amino acids through the production of the aglycone analogue of keratinimicin A, a GPA that is 5-fold more potent than vancomycin against . In the course of these studies, we found that the cytochrome P450 enzyme OxyB boasts both broad substrate tolerance and remarkable selectivity in the formation of the first aryl ether cross-link on the linear peptide precursors. The X-ray crystal structure of OxyB, determined to 2.8 Å, points to structural features that may contribute to these properties. Our results set the stage for using OxyB broadly as a biocatalyst toward the chemoenzymatic synthesis of diverse GPA analogues.

PubMed: 37405871
DOI: 10.1021/acschembio.3c00192

実験手法

X-RAY DIFFRACTION (2.8 Å)