Oxidase enzymes as sustainable oxidation catalysts

Abstract

Oxidation is one of the most important processes used by the chemical industry. However, many of the methods that are used pose significant sustainability and environmental issues. Biocatalytic oxidation offers an alternative to these methods, with a now significant enzymatic oxidation toolbox on offer to chemists. Oxidases are one of these options, and as they only depend on molecular oxygen as a terminal oxidant offer perfect atom economy alongside the selectivity benefits afforded by enzymes. This review will focus on examples of oxidase biocatalysts that have been used for the sustainable production of important molecules and highlight some important processes that have been significantly improved through the use of oxidases. It will also consider emerging classes of oxidases, and how they might fit in a future biorefinery approach for the sustainable production of important chemicals.

Keywords: alcohol oxidation; amine oxidation; biocatalysis; oxidases; sustainable oxidation.

Scheme 1.

Biocatalytic approaches to oxidation are commonly undertaken with oxidases or dehydrogenases, X = OH, NH_2.

Scheme 2.

Catalytic cycle of copper-containing oxidases [10].

Scheme 3.

Aldehyde oxidation to carboxylic acid via gem-diol intermediate.

Scheme 4.

PEF production from sugars via HMF and FDCA.

Scheme 5.

Engineered GOase variant for oxidative desymmetrization of glycerol intermediate for islatravir synthesis.

Scheme 6.

Catalytic cycle of flavin-containing AOx [10].

Scheme 7.

Two-step oxidation of choline by choline oxidase yielding betaine.

Scheme 8.

Reported substrate scope of AcO6 [a] in vivo.

Figure 1.

Proposed model for the binding of 5-hydroxymethylfurfural substrate in HMFO active site. Reprinted with permission from Mattevi et al. [39]. Copyright 2015 American Chemical Society.

Scheme 9.

Biocatalytic deracemization process using MAO-N.

Scheme 10.

Three-step synthesis of (R)-2-phenylpyrrolidine using a chemoenzymatic deracemization.

Scheme 11.

Different molecules synthesized with MAO-N variants.

Scheme 12.

Boceprevir and the fragment synthesized using an engineered AmOX.

Scheme 13.

Two-stage chemoenzymatic pyrrole synthesis with Grubbs-II catalyst and 6-HDNO.

Scheme 14.

Biocatalytic cascade synthesis of islatravir. Enzymes in blue were engineered in the study [28]. GOase = galactose oxidase, HRP = horseradish peroxidase, PanK = pantothenate kinase, DERA = deoxyribose 5-phosphate aldolase, PPM = phosphopentamutase, PNP = purine nucleoside phosphorylase.

Figure 2.

Structure of cellulose with glycosidic cleavage points for canonical exo- and endo-cellulase activity.

Figure 3.

Oxidative cleavage of glycosidic linkages by LPMOS (C4 cleavage shown).

Figure 4.

(a) Three-dimensional structure of a typical LPMO and (b) histidine brace complex coordinating active site Cu^II (adapted with permission from reference [63]).