Genome Mining for New Enzyme Chemistry

Abstract

A revolution in the field of biocatalysis has enabled scalable access to compounds of high societal values using enzymes. The construction of biocatalytic routes relies on the reservoir of available enzymatic transformations. A review of uncharacterized proteins predicted from genomic sequencing projects shows that a treasure trove of enzyme chemistry awaits to be uncovered. This Review highlights enzymatic transformations discovered through various genome mining methods and showcases their potential future applications in biocatalysis.

Non-Canonical Tryptophan Synthesis Enabled by Larock Umpolung

“…Zosurabalpin, for example, is a tryptophan-containing macrocyclic antimicrobial drug developed recently for the treatment of carbapenem-resistant Acinetobacter baumannii infections 9 . More recently, aromatic ring modified tryptophan derivatives containing C-C, C-N and C-O cross-links have been identified in peptide natural products 10 . Darobactin and tryglysin are ribosomally synthesized and post-translationally modified peptides (RiPPs) that possess intricate ring structures and potent antimicrobial activities [11][12][13] .…”

“…Darobactin and tryglysin are ribosomally synthesized and post-translationally modified peptides (RiPPs) that possess intricate ring structures and potent antimicrobial activities [11][12][13] . Due to the wide occurrence and importance of tryptophan, chemical modification on C4-C7 of the indole moiety occurs either naturally or artificially to drastically alter its chemical and functional properties [1][2][3]7,8,10 . 5-Hydroxylation of tryptophan is the initial step for the biosynthesis of serotonin and melatonin, hormones that mediate the sleep-wake cycle in vertebrates 1 .…”