Enzymatic Regio- and Enantioselective C–H Oxyfunctionalization of Fatty Acids

This is the authors' abstract. We don't add key points for this paper.

Directed evolution of a P450 hydroxylase (P450 BSβ ) 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 H 2 O 2 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.