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.

Automated summary

The ability to selectively modify functional groups in a molecule can simplify syntheses and increase yields. Enzymes can catalyze site-selective transformations, but using this capability for non-native substrates and reactions requires understanding of enzymatic catalysis and protein engineering. This review discusses examples of site-selective enzyme catalysis involving functional group manipulation and C-H bond functionalization, focusing on cases with non-native substrates and engineered enzymes. The review also explores the use of these enzymes in chemoenzymatic transformations and target-oriented synthesis, and provides an overview of tools and techniques to expand the scope of non-native site-selective enzyme catalysis.