tRNA-dependent amide bond-forming enzymes in peptide natural product biosynthesis

Abstract

In the ribosome-independent biosynthesis of peptide natural products, amino acid building blocks are generally activated in the form of phosphoesters, esters, or thioesters prior to amide bond formation. Following the recent discovery of bacterial enzymes that utilize an aminoacyl ester with a transfer ribonucleic acid (tRNA) in primary metabolism, the number of tRNA-dependent enzymes used in biosynthetic studies of peptide natural products has increased steadily. In this review, we summarize the rapidly growing knowledge base regarding two types of tRNA-dependent enzymes, which are structurally and functionally distinct. Initially, we focus on enzymes with the GCN5-related N-acetyltransferase fold and discuss the catalytic function and aminoacyl-tRNA recognition. Next, newly found peptide-amino acyl tRNA ligases and their ATP-dependent reactions are highlighted.

Keywords: Amide bond; Biosynthesis; FemX; Natural product; PEARLs; Peptide; tRNA.