Abstract
Resorcinomycin (1) is composed of a nonproteinogenic amino acid, (S)-2-(3,5-dihydroxy-4-isopropylphenyl)-2-guanidinoacetic acid (2), and glycine. A biosynthetic gene cluster was identified in a genome database of Streptoverticillium roseoverticillatum by searching for orthologs of the genes responsible for biosynthesis of pheganomycin (3), which possesses a (2)-derivative at its N-terminus. The cluster contained a gene encoding an ATP-grasp-ligase (res5), which was suggested to catalyze the peptide bond formation between 2 and glycine. A res5-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 N-terminus may be used as a nucleophile and then maturated by a peptidase encoded by a gene outside of the cluster.
Graphical abstract
Biosynthetic gene cluster of resorcinomycin composed of (S)-2-(3,5-dihydroxy-4-isopropylphenyl)-2-guanidinoacetic acid and glycine was identified and characterized
![](/cms/asset/5495f108-7f1f-4082-9592-57a09ae62fa9/tbbb_a_1050992_uf0001_oc.jpg)
Acknowledgments
This study was supported by Grants-in-Aid for Scientific Research (23108101 and 25560397 to T. Dairi) from the Japan Society for the Promotion of Science (JSPS). We also thank Shinogi & Co. Ltd., Osaka, Japan, for providing Streptoverticillium roseoverticillatum and the resorcinomycin A standard.