Recent Advances in the Substrate Selectivity of Aldolases

Aldolases are powerful C–C bond-forming enzymes in biocatalysis because of their unparalleled stereoselectivity, the ease with which reactions that do not require cofactor recycling can be set up, the large number of different types and families available, and reaction feasibility under mild operating conditions. Since 2016, major discoveries have been made that broaden the scope of both nucleophile and electrophile substrates. For instance, more hydrophobic, sterically hindered nucleophile components have led to structures that are difficult to synthesize with purely chemical procedures. Likewise, the use of structurally diverse ketones as electrophiles has allowed the stereoselective synthesis of tertiary alcohols. These major advances will be presented and discussed in this Review.