Enzymatic Regio- and Enantioselective C–H Oxyfunctionalization of Fatty Acids
Hao Chen, Mengfei Huang, Wenliang Yan, Wen‐Ju Bai, Xiqing Wang
Abstract
Directed evolution of a P450 hydroxylase (P450BSβ) achieves an engineered enzyme that is able to catalyze C–H oxyfunctionalization of fatty acids (FAs) in a highly regio- and enantioselective fashion (>20:1 Cβ/Cα and > 99% ee in all cases). The biocatalyst displays high reactivity (TON up to 1540), takes inexpensive H2O2 as oxidant, and converts C11–C18 saturated FAs as well as naturally derived unsaturated oleic and linoleic acids to optically pure β-hydroxy FAs. Merging biocatalysis with chemical transformation, we further offer a chemoenzymatic strategy to access valuable FA derivatives bearing 1,3-diol, β-amino, β-lactone, and β-lactam functionalities in either enantiomeric form. Molecular docking studies provide a rationale for the regio- and enantioselectivity of this reaction.