title: Identification and analysis of the resorcinomycin biosynthetic gene cluster.
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.
authors.affiliation: a Graduate School of Engineering , Hokkaido University , Sapporo , Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ooya
authors.affiliation: a Graduate School of Engineering , Hokkaido University , Sapporo , Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ogasawara
authors.affiliation: a Graduate School of Engineering , Hokkaido University , Sapporo , Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Noike
authors.affiliation: a Graduate School of Engineering , Hokkaido University , Sapporo , Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Dairi
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism; D016681:Genome, Fungal; D005998:Glycine / Q000737:chemistry; D008025:Ligases / Q000737:chemistry* / Q000378:metabolism; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D004151:Dipeptides; D010455:Peptides; C000595498:pheganomycin; C058733:resorcinomycin A; D008025:Ligases; D005998:Glycine
keywords: ATP-grasp-ligase; Streptoverticillium roseoverticillatum; biosynthesis; resorcinomycin