Discovery, engineering, and applications of amino acid and peptide prenyltransferases

Abstract

Amino acid and peptide prenylation leads to a large variety of natural products, including neurotoxins, alkaloids and (non-)ribosomal peptides, with potent bioactivities. The key biosynthetic enzymes are structurally diverse prenyltransferases, which attach short, linear prenyl donors to amino acid acceptor substrates, and show impressive regio- and chemo-selectivity. The emerging number of characterized prenyltransferases, along with their scope, promiscuity, and engineering, provides an expanded chemoenzymatic toolbox for amino acid prenylation and peptide late-stage functionalization with potential in industrial applications such as peptide-based drug development.