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Nucleophile Promiscuity of Natural and Engineered Aldolases
Karel Hernández1, Anna Szekrenyi2, Pere Clapés1
1Department of Chemical Biology and Molecular Modelling, Catalonia Institute for Advanced Chemistry IQAC-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain.
Abstract:
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.
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