P450 cyptide synthase MpoB catalyzes the cross-linking of the YPW motif on the precursor peptide

Cytochrome P450 enzymes in ribosomally synthesized and post-translationally modified peptides (RiPPs) catalyze C-C, C-N, or C-O cross-linking reactions in the biosynthesis of biaryl cyclophane natural products. Here, we manually identified 127 homologous P450s linked to putative precursor peptides containing the YPW motif. Through <i>in vivo</i> functional studies in <i>Escherichia coli</i>, the newly identified enzyme MpoB from <i>Micromonospora polyrhachis</i> DSM 45886 was found to catalyze the formation of a cross-link between Tyr-C3 and Trp-N1 at the YPW motif. This result provides an additional toolkit for cross-linked peptide modification.