Recent advances of structure, function, and engineering of carboxylesterases for the pharmaceutical industry: A minireview

Abstract

Carboxylesterases have a wide range of applications due to their catalytic efficiency, robust structure, and broad substrate specificity. These enzymes, which can hydrolyze carboxylic acid esters, amides, and thioesters, stand out with their regio- and enantioselective properties. They play a crucial role in synthesizing pharmaceutical intermediates, including secondary and tertiary alcohols, α-hydroxy acids, and various bioactive compounds. However, in some cases, the enantioselectivity of carboxylesterases may be insufficient to achieve conversions with the purity required by the pharmaceutical industry. This review summarizes the crucial role of carboxylesterases, particularly in the pharmaceutical field, focusing on the classification, structure, and engineering approaches. After introducing the main families of carboxylesterases, the structural studies are presented to give a comprehensive insight into the active site architecture and related key determinants for enantioselectivity. The protein engineering studies to improve the enantioselectivity of carboxylesterases are discussed along with solvent engineering and immobilization applications.

Keywords: Cap domain; Carboxylesterase; Enantioselectivity; Engineering strategies; Pharmaceuticals; α/β-Hydrolase fold.