Issue 12, 2020

Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols

Abstract

We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99% conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected C[double bond, length as m-dash]C bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99% conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85% isolated yield.

Graphical abstract: Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols

Supplementary files

Article information

Article type
Paper
Submitted
10 Mar 2020
Accepted
24 Apr 2020
First published
01 Jun 2020
This article is Open Access
Creative Commons BY license

Green Chem., 2020,22, 3927-3939

Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols

G. A. Aleku, G. W. Roberts and D. Leys, Green Chem., 2020, 22, 3927 DOI: 10.1039/D0GC00867B

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