title: Identification of a putative FR901469 biosynthesis gene cluster in fungal sp. No. 11243 and enhancement of the productivity by overexpressing the transcription factor gene frbF.
abstract: FR901469 is an antifungal antibiotic produced by fungal sp. No. 11243. Here, we searched for FR901469 biosynthesis genes in the genome of No. 11243. Based on the molecular structure of FR901469 and endogenous functional motifs predicted in each genomic NRPS gene, a putative FR901469 biosynthesis gene cluster harboring the most plausible NRPS gene was identified. A transcription factor gene, designated frbF, was found in the cluster. To improve FR901469 productivity, we constructed a strain in which frbF was overexpressed and named it TFH2-2. FR901469 productivity of TFH2-2 was 3.4 times higher than that of the wild-type strain. Transcriptome analysis revealed that most of the genes in the putative FR901469 biosynthesis gene cluster were upregulated in TFH2-2. It also showed that the expression of genes related to ergosterol biosynthesis, β-1,3-glucan catabolism, and chitin synthesis was inclined to exhibit significant differences in TFH2-2.
authors.affiliation: Biotechnology Labs, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan; Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan. Electronic address: makoto.matsui@astellas.com.
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsui
authors.affiliation: Biotechnology Labs, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan; Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nemoto
authors.affiliation: Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan; Fermlab, Inc., 4-3-1-913 Shirakawa, Koto-ku, Tokyo 135-0021, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: INTEC Inc, 1-3-3 Shinsuna Koto-ku, Tokyo 136-8637, Japan; Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Terai
authors.affiliation: Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan; Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamano
authors.affiliation: Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan; Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Machida
authors.affiliation: Biotechnology Labs, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan; Technology Research Association of Highly Efficient Gene Design (TRAHED), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000378:metabolism; D003001:Cloning, Molecular; D047630:Depsipeptides / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D005810:Multigene Family; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D055666:Lipopeptides
chemical_list: D000935:Antifungal Agents; D047630:Depsipeptides; D005656:Fungal Proteins; D014157:Transcription Factors; C417112:FR 901469; D055666:Lipopeptides
keywords: FR901469; Fungal sp. No. 11243; Genomic analysis; Secondary metabolite; Transcriptome