Non-Native Site-Selective Enzyme Catalysis

Theability to site-selectively modify equivalent functional groupsin a molecule has the potential to streamline syntheses and increaseproduct yields by lowering step counts. Enzymes catalyze site-selectivetransformations throughout primary and secondary metabolism, but leveragingthis capability for non-native substrates and reactions requires adetailed understanding of the potential and limitations of enzymecatalysis and how these bounds can be extended by protein engineering.In this review, we discuss representative examples of site-selectiveenzyme catalysis involving functional group manipulation and C-Hbond functionalization. We include illustrative examples of nativecatalysis, but our focus is on cases involving non-native substratesand reactions often using engineered enzymes. We then discuss theuse of these enzymes for chemoenzymatic transformations and target-orientedsynthesis and conclude with a survey of tools and techniques thatcould expand the scope of non-native site-selective enzyme catalysis.