Increasing cytochrome P450 enzyme diversity by identification of two distinct cyclodipeptide dimerases

Abstract

Genome mining revealed the presence of two cdps-p450 operons in Saccharopolyspora antimicrobica. Heterologous expression, biochemical characterisation and structure elucidation proved that the two P450 enzymes catalyse distinct regio- and stereospecific dimerizations of cyclo-(l-Trp-l-Trp), which significantly expands the repertoire of diketopiperazine-tailoring enzymes. TtpB1 connects the monomers via C3-C3', both from the opposite side of H-11/H-11', while TtpB2 is characterised as the first P450 to mainly catalyse the unusual linkage between N1' and C3 from the H-11 side.

Topics & Concepts