7WYG

Crystal structure of P450BSbeta-L78I/Q85H/G290I variant in complex with palmitic acid.

Summary for 7WYG

• Entry DOI: 10.2210/pdb7wyg/pdb
• Descriptor: Cytochrome P450 152A1, PROTOPORPHYRIN IX CONTAINING FE, PALMITOLEIC ACID, ... (6 entities in total)
• Functional Keywords: cytochrome p450, oxidoreductase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 2
• Total formula weight: 99624.24

Authors

Li, F.,He, C.,Wang, X. (deposition date: 2022-02-16, release date: 2022-12-21, Last modification date: 2023-11-29)

Primary citation

Zhang, K.,Yu, A.,Chu, X.,Li, F.,Liu, J.,Liu, L.,Bai, W.J.,He, C.,Wang, X.
Biocatalytic Enantioselective beta-Hydroxylation of Unactivated C-H Bonds in Aliphatic Carboxylic Acids.
Angew.Chem.Int.Ed.Engl., 61:e202204290-e202204290, 2022

PubMed Abstract: Catalytic selective hydroxylation of unactivated aliphatic (sp ) C-H bonds without a directing group represents a formidable task for synthetic chemists. Through directed evolution of P450 hydroxylase, we realize oxyfunctionalization of unactivated C-H bonds in a broad spectrum of aliphatic carboxylic acids with varied chain lengths, functional groups and (hetero-)aromatic moieties in a highly chemo-, regio- and enantioselective fashion (>30 examples, Cβ/Cα>20 : 1, >99 % ee). The X-ray structure of the evolved variant, P450 -L78I/Q85H/G290I, in complex with palmitic acid well rationalizes the experimentally observed regio- and enantioselectivity, and also reveals a reduced catalytic pocket volume that accounts for the increased reactivity with smaller substrates. This work showcases the potential of employing a biocatalyst to enable a chemical transformation that is particularly challenging by chemical methods.

PubMed: 35536725
DOI: 10.1002/anie.202204290

Experimental method

X-RAY DIFFRACTION (2 Å)