Identification and analysis of the resorcinomycin biosynthetic gene cluster

<div><p>Resorcinomycin (1) is composed of a nonproteinogenic amino acid, (<i>S</i>)-2-(3,5-dihydroxy-4-isopropylphenyl)-2-guanidinoacetic acid (2), and glycine. A biosynthetic gene cluster was identified in a genome database of <i>Streptoverticillium roseoverticillatum</i> by searching for orthologs of the genes responsible for biosynthesis of pheganomycin (3), which possesses a (2)-derivative at its <i>N</i>-terminus. The cluster contained a gene encoding an ATP-grasp-ligase (<i>res5</i>), which was suggested to catalyze the peptide bond formation between 2 and glycine. A <i>res5</i>-deletion mutant lost 1 productivity but accumulated 2 in the culture broth. However, recombinant RES5 did not show catalytic activity to form 1 with 2 and glycine as substrates. Moreover, heterologous expression of the cluster resulted in accumulation of only 2 and no production of 1 was observed. These results suggested that a peptide with glycine at its <i>N</i>-terminus may be used as a nucleophile and then maturated by a peptidase encoded by a gene outside of the cluster.</p></div>