Arylmalonate Decarboxylase—A Versatile Biocatalyst for the Synthesis of Optically Pure Carboxylic Acids

Anna K Schweiger,Kenji Miyamoto,Robert Kourist

doi:10.3389/fctls.2021.742024

Abstract

Bacterial arylmalonate decarboxylase (AMDase) is an intriguing cofactor-independent enzyme with a broad substrate spectrum. Particularly, the highly stereoselective transformation of diverse arylmalonic acids into the corresponding chiral α-arylpropionates has contributed to the broad recognition of this biocatalyst. While, more than 30 years after its discovery, the native substrate and function of AMDase still remain undiscovered, contributions from multiple fields have ever since brought forth a powerful collection of AMDase variants to access a wide variety of optically pure α-substituted propionates. This review aims at providing a comprehensive overview of the development of AMDase from an enzyme with unknown function up to a powerful tailored biocatalyst for the synthesis of industrially relevant optically pure α-arylpropionates. Historical perspectives as well as recent achievements in the field will be covered within this work.

Highlights

Arylmalonate decarboxylase (AMDase, EC 4.1.1.76), originally isolated from the soil bacterium Bordetella bronchiseptica, catalyzes the decarboxylation of α-aromatic- or α-alkenylmalonic acids to yield the corresponding optically pure mono-acid without the aid of a cofactor
Miyamoto et al discovered arylmalonate decarboxylase (AMDase) in the 1990’s in a screening to identify enzymes for the generation of chiral molecules from prochiral malonates by enzymatic decarboxylation (Miyamoto Ohta and, Hiromichi, 1990; Miyamoto and Ohta, 1992a) As the decarboxylation of malonyl-ACP is a key step in metabolism, it appeared likely that the bacterial catabolism might possess malonate decarboxylases
By consulting the grid inhomogeneous solvation theory (GIST) (Nguyen et al, 2012; Nguyen et al, 2014) to analyze the local hydrophobicity within the AMDase active site, we found clear evidence for a mechanism driven by ground-state destabilization by entrapment of the carboxylate to-be-cleaved in a hydrophobic environment

Summary

Introduction

Arylmalonate decarboxylase (AMDase, EC 4.1.1.76), originally isolated from the soil bacterium Bordetella bronchiseptica, catalyzes the decarboxylation of α-aromatic- or α-alkenylmalonic acids to yield the corresponding optically pure mono-acid without the aid of a cofactor. The unique reactivity and broad substrate tolerance allows for the production of diverse aryl- or alkenylaliphatic carboxylic acids in outstanding optical purity, amongst them several α-arylpropionates with non-steroidal antiinflammatory activity, the so-called profens (Miyamoto and Kourist, 2016). Miyamoto et al discovered arylmalonate decarboxylase (AMDase) in the 1990’s in a screening to identify enzymes for the generation of chiral molecules from prochiral malonates by enzymatic decarboxylation (Miyamoto Ohta and, Hiromichi, 1990; Miyamoto and Ohta, 1992a) As the decarboxylation of malonyl-ACP is a key step in metabolism, it appeared likely that the bacterial catabolism might possess malonate decarboxylases. The screening followed the assumption that decarboxylation of α-phenylmalonic acid 1a could represent the initial step in the metabolism, followed

Objectives

Findings

Conclusion