Gene-guided discovery and engineering of branched cyclic peptides in plants

Significance In the past decade, the number of publicly available plant genomes and transcriptomes has steadily increased. Inspired by this genetic resource, we developed a genome-mining approach for the rapid discovery of plant ribosomal peptides from genome-sequenced plants. Herein, we introduce the hypotensive lyciumins as a class of branched cyclic ribosomal peptides in plants and show that they are widely distributed in crop and forage plants. Our results suggest that lyciumin biosynthesis is coupled to plant-specific BURP domains in their precursor peptides and that lyciumin peptide libraries can be generatedin planta . This discovery sets the stage for gene-guided discovery of peptide chemistry in the plant kingdom and therapeutic and agrochemical applications of lyciumins.