title: Functional analysis of hatomarubigin biosynthesis genes and production of a new hatomarubigin using a heterologous expression system.
abstract: The function of hatomarubigin biosynthesis genes was analyzed by heterologous expression of the hrb gene cluster. Streptomyces lividans carrying a gene cluster consisting of 25 genes (hrbR1-hrbX) with hrbY was found to produce all the known hatomarubigins including hatomarubigin D, which has a unique dimeric angucycline with a methylene linkage. Gene disruption was used in this heterologous expression system to analyze the function of hrbF, a gene with no homology to any known angucycline biosynthesis genes. A new metabolite was detected in the fermented broth of S. lividans expressing the hrb genes lacking hrbF and was designated hatomarubigin F. This compound was identified as 5-hydroxyhatomarubigin E by NMR spectroscopic analysis, suggesting that HrbF regulates the regiospecificity of oxygenation enzymes.
authors.affiliation: Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Izawa
authors.affiliation: Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kimata
authors.affiliation: Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hayakawa
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism*; D005285:Fermentation; D015870:Gene Expression; D005798:Genes, Bacterial / Q000502:physiology*; D005810:Multigene Family; D010100:Oxygen / Q000378:metabolism; D048170:Streptomyces lividans / Q000201:enzymology* / Q000235:genetics
chemical_list: C587970:5-hydroxyhatomarubigin E; D000880:Anthraquinones; C587971:hatomarubigin F; D010100:Oxygen