Nucleophile Promiscuity of Natural and Engineered Aldolases

• Published in: Chembiochem : a European journal of chemical biology Vol. 19; no. 13; pp. 1353 - 1358
• Main Authors: Hernández, Karel, Szekrenyi, Anna, Clapés, Pere
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 04-07-2018
• Subjects: Aldehyde-Lyases - chemistry; Aldehyde-Lyases - genetics; Aldehydes; aldol reaction; Amino Acids - chemistry; Amino Acids - genetics; asymmetric synthesis; Biocatalysis; Biocatalysts; Carbon; Catalysts; Catalytic Domain - genetics; enzymes; Gram-Negative Bacteria - enzymology; Manufacturing industry; Mutagenesis, Site-Directed - methods; Mutation; Organic chemistry; Protein engineering; Proteins; Stereoisomerism; Substrates; aldol reaction; enzymes; protein engineering; asymmetric synthesis; biocatalysis
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201800135

The asymmetric aldol addition reaction mediated by aldolases is recognized as a green and sustainable method for carbon–carbon bond formation. Research in this area has unveiled their unprecedented synthetic potential toward diverse, new chemical structures; novel product families; and even as a technology for industrial manufacturing processes. Despite these advances, aldolases have long been regarded as strictly selective catalysts, particularly for nucleophilic substrates, which limits their broad applicability. In recent years, advances in screening technologies and metagenomics have uncovered novel C−C biocatalysts from superfamilies of widely known lyases. Moreover, protein engineering has revealed the extraordinary malleability of different carboligases to offer a toolbox of biocatalysts active towards a large structural diversity of nucleophile substrates. Herein, the nucleophile ambiguity of native and engineered aldolases is discussed with recent examples to prove this novel concept.
Open to change: The asymmetric aldol addition reaction mediated by aldolases is a green and sustainable way for carbon–carbon bond formation. Recent investigations in this field show the extraordinary nucleophile flexibility of native and engineered aldolases to offer a toolbox of biocatalysts for the synthesis of diverse new chemical structures and product families.