Enantioselective oxidation of secondary alcohols by the flavoprotein alcohol oxidase from Phanerochaete chrysosporium

Gwen Tjallinks,Caterina Martin,Marco W Fraaije

doi:10.1016/j.abb.2021.108888

Abstract

The enantioselective oxidation of secondary alcohols represents a valuable approach for the synthesis of optically pure compounds. Flavoprotein oxidases can catalyse such selective transformations by merely using oxygen as electron acceptor. While many flavoprotein oxidases preferably act on primary alcohols, the FAD-containing alcohol oxidase from Phanerochaete chrysosporium was found to be able to perform kinetic resolutions of several secondary alcohols. By selective oxidation of the (S)-alcohols, the (R)-alcohols were obtained in high enantiopurity. In silico docking studies were carried out in order to substantiate the observed (S)-selectivity. Several hydrophobic and aromatic residues in the substrate binding site create a cavity in which the substrates can comfortably undergo van der Waals and pi-stacking interactions. Consequently, oxidation of the secondary alcohols is restricted to one of the two enantiomers. This study has uncovered the ability of an FAD-containing alcohol oxidase, that is known for oxidizing small primary alcohols, to perform enantioselective oxidations of various secondary alcohols.

Highlights

The outstanding selectivity of enzymes allows them to catalyse re actions that are difficult to accomplish in a chemocatalytic manner [1,2,3]
Several strategies have been developed in order to obtain enantiopure alcohols using a biocatalytic approach, which include enantioselective reduction of prochiral ketones [4] and enzyme-catalysed kinetic resolutions of secondary alcohols [5]
Alcohol oxidases are a subclass of oxidases and contain either a flavin adenine dinucleotide (FAD) or copper as pros thetic group

Summary

Introduction

The outstanding selectivity of enzymes allows them to catalyse re actions that are difficult to accomplish in a chemocatalytic manner [1,2,3]. We investigated the selective oxidative abilities of a flavoprotein alcohol oxidase towards secondary alcohols. This is a striking discovery, as there have not yet been many flavin-dependent AOXs reported that are active on secondary alcohols. Various secondary alcohols and AOX variants were probed for their ability to perform kinetic resolutions.

Results

Conclusion