Macrocyclic antibiotics production-platform through biosynthetic engineering

2011 Fiscal Year Final Research Report

• Project/Area Number: 21360404
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: Osaka University
• Principal Investigator: NIHIRA Takuya 大阪大学, 生物工学国際交流センター, 教授 (70144441)
• Co-Investigator(Kenkyū-buntansha): KINOSHITA Hiroshi 大阪大学, 生物工学国際交流センター, 助教 (20294035) ; KITANI Shigeru 大阪大学, 生物工学国際交流センター, 助教 (10379117)
• Project Period (FY): 2009 – 2011
• Keywords: 生体触媒工学 / 二次代謝 / 生理活性物質 / 生合成制御

Research Abstract

Among the useful microorganisms on which whole genome information is available, as the host having high potential for the production of bioactive compounds, Streptomyces avermitilis for prokaryotes and As pergillus oryzae for eukaryotes were developed as the basic expression hosts. A novel Streptomyces hormone controlling secondary metabolites in S. avermitilis was isolated and its structure was elucidated for the first time in the world, together with finding many regulatory genes and identification of their functions. With A. oryzae, new expression host harboring a novel gene upregulating secondary metabolism was developed, and system to correlate biosynthetic gene cluster with products was successfully developed.

Research Products

• [Journal Article] Kitasetaline, a novelβ-carboline alkaloid from Kitasatospora setae NBRC 14216^T (2012)
  • Author(s): Aroonsri, A., Kitani, S., Ikeda, H. and Nihira. T.
  • Journal Title: J. Bioeng. Biotechnol Volume: (In Press)
• [Journal Article] Identification and characterization of Penicillium citrinum VeA and LaeA as global regulators for ML-236B production (2011)
  • Author(s): Baba, S., Kinoshita, H. and Nihira, T.
  • Journal Title: Current Genetics Volume: 58 Pages: 1-11
• [Journal Article] Sarmentosamide, a novel hexadienamide from Thai soil actinomycetes (2011)
  • Author(s): Kitani, S., Tomio, A., Srichaisupakit, A., Intra, B., Panbangred, W., Oku, N., Igarashi, Y. and Nihira, T.
  • Journal Title: Nat Pro Res Volume: (In press)
• [Journal Article] Prajinamide, a new modified peptide from a soil-derived Streptomyces (2011)
  • Author(s): Igarashi, Y., Tanaka, Y., Ikeda, M., Oikawa, T., Kitani, S., Nihira, T., Mongkol, P., Janhom, M., and Panbangred, W.
  • Journal Title: J. Antibiotics Nature Volume: (In press)
• [Journal Article] Heterologous expression system in Aspergillus oryzae for fungal biosynthetic gene clusters of secondary metabolites (2011)
  • Author(s): Sakai, K., Kinoshita, H., and Nihira, T.
  • Journal Title: Appl. Microbiol. Biotechnolo. Volume: 93
• [Journal Article] Total synthesis and absolute configuration of avenolide, extracellular factor in Streptomyces avermitilis (2011)
  • Author(s): Nagamitsu, T., Uchida, M., Takamatsu, S., Arima, S. Miyamoto, K., Kitani, S. Nihira, T. and Ikeda, H.
  • Journal Title: J. Antibiotics Nature Volume: 64 Pages: 781-787
• [Journal Article] Avenolide, a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis (2011)
  • Author(s): Kitani, S, Miyamoto, K T, Takamatsu, S, Herawati, E, Iguchi, H, Nishimoto, K, Uchida, M, Nagamitsu, T, . mura, S, Ikeda, H and Nihira, T.
  • Journal Title: Proc. Natl. Acad. Sci. Volume: 108 Pages: 16410-5
• [Journal Article] VisG is essential for biosynthesis of virginiamycin S, a streptogramin type B antibiotic, as a provider of the nonproteinogenic amino acid phenylglycine (2011)
  • Author(s): Fitrianingsih, Kitani, S., Fukushima, E. and Nihira, T.
  • Journal Title: Microbiology Volume: 157 Pages: 3213-3220
• [Journal Article] The autoregulator-receptor homologue AvaR3 plays a regulatory role in antibiotic production, mycelial aggregation and colony development of Streptomyces avermitilis (2011)
  • Author(s): Miyamoto, K., Kitani, S., Komatsu, M., Ikeda, H. and Nihira, T.
  • Journal Title: Microbiology Volume: 157 Pages: 2266-75
• [Journal Article] Identification of actinomycetes from plant rhizospheric soils with inhibitory activity against Colletotrichum spp., the causative agent of anthracnose disease (2011)
  • Author(s): Intra B, Mungsuntisuk I, Nihira T, Igarashi Y, Panbangred W.
  • Journal Title: BMC Res. Notes Volume: 4 Pages: 98
• [Journal Article] Xylaropyrone, a newγ-pyrone from the endophytic fungus Xylaria feejeensis MU18 (2010)
  • Author(s): Siriwach, R., Kinoshita, H., Kitani, S., Igarashi, Y., Pansuksan, K., Panbangred, W., Nihira, T.
  • Journal Title: Journal of Antibiotics Nature Volume: 64 Pages: 217-219
• [Journal Article] Characterization of varM encoding type II ABC transporter in Streptomyces virginiae, a virginiamycin M_1 producer (2010)
  • Author(s): Kitani, S., Yamauchi, T., Fukushima, E., Lee, C. K, Fitria Ningsih, Kinoshita, H., and Nihira, T.
  • Journal Title: Actinomycetologica Volume: (In press)
• [Journal Article] Identification and characterization of soil-isolated Streptomyces SJE177 producing actinomycin (2010)
  • Author(s): Euanorasetr, J., Nilvongse, A., Tantimavanich, S., Nihira, T., Igarashi, Y., Panbangred, W.
  • Journal Title: Southeast Asian J Trop Med Public Health Volume: 41 Pages: 1177-1187
• [Journal Article] Crystallization and preliminary crystallographic studies of the butyrolactone autoregulator receptor protein(BarA) from Streptomyces virginiae (2010)
  • Author(s): Yoon, Y-H., Kawai, F., Sugiyama, K., Park, S-Y., Nihira, T., Choi, S-U., and Hwang, Y-I.
  • Journal Title: Structural Biology and Crystallization Communications Volume: 66 Pages: 662-664
• [Journal Article] Genome Sequence of Kitasatospora setae NBRC 14216T : An Evolutionary Snapshot of the Family Streptomycetaceae (2010)
  • Author(s): Ichikawa, N., Oguchi, A., Ikeda, H., Ishikawa, J., Kitani, S., Watanabe, Y., Nakamura, S., Katano, Y., Kishi, E., Sasagawa, M., Ankai, A., Fukui, S., Hashimoto, Y., Kamata, S., Otoguro, M., Tanikawa, S., Nihira, T., Horinouchi, S., Ohnishi, Y., Hayakawa, M., Kuzuyama, T., Arisawa, A., Nomoto, F., Miura, H., Takahashi, Y., and Fujita, N.
  • Journal Title: DNA Research Volume: 17 Pages: 393-406
• [Journal Article] Rakicidin D, an inhibitor of tumor cell invasion from marine-derived Streptomyces sp. (2010)
  • Author(s): Igarashi, Y., Shimasaki, R., Miyanaga, S., Oku, N., Onaka, H., Sakurai, H., Saiki, I., Kitani, S., Nihira, T., Panbangred, W., and Wimonsiravude, W.
  • Journal Title: J. Antibiotics Volume: 63 Pages: 563-565
• [Journal Article] Cloning and functional analysis of the second geranylgeranyl diphosphate synthase gene influeicing helvolic acid biosynthesis in Metarhizium anisopliae (2010)
  • Author(s): Singkaravanit, S., Kinoshita, H., Ihara, F., and Nihira, T.
  • Journal Title: Appl. Microbiol. Biotechnol Volume: 87 Pages: 1077-1088
• [Journal Article] Control of secondary metabolism by farX, which is involved in theγ-butyrolactone biosynthesis of Streptomyces lavendulae FRI-5 (2010)
  • Author(s): Kitani, S., Doi, M., Shimizu, T., Maeda, A., and Nihira, T.
  • Journal Title: Arch Microbiol Volume: 192 Pages: 211-220
• [Journal Article] Ophiosetin, a New Tetramic Acid Derivative from the Mycopathogenic Fungus Elaphocordyceps ophioglossoides (2010)
  • Author(s): Sastia, P. Putri, Kinoshita, H., Ihara, F., Igarashi, Y. and Nihira, T.
  • Journal Title: J. Antibiotics Nature Volume: 63 Pages: 195-198
• [Journal Article] Null mutation analysis of an afsA-family gene, barX, that is involved in biosynthesis of theγ-butyrolactone autoregulator in Streptomyces virginiae (2010)
  • Author(s): Lee, Y-J., Kitani, S. and Nihira, T.
  • Journal Title: Microbiology Volume: 156 Pages: 206-10
• [Journal Article] Geranylgeranyl diphosphate synthase genes in entomopathogenic fungi (2010)
  • Author(s): Singkaravanit, S., Kinoshita, H., Ihara, F. and Nihira, T.
  • Journal Title: Appl. Microbiol. Biotechnol. Volume: 85 Pages: 1463-1472
• [Journal Article] Farinomalein, a Maleimide-bearing Compound from the Entomopathogenic Fungus Paecilomyces farinosus (2009)
  • Author(s): Sastia P. Putri, Kinoshita, H., Ihara, F., Igarashi, Y. and Nihira, T.
  • Journal Title: J. Natural Products Volume: 72 Pages: 1544-6
• [Journal Article] Analysis of Two Additional Signaling Molecules in Streptomyces coelicolor and the Development of a Novel (2009)
  • Author(s): Hsiao, N-H., Nakayama, S., Merlo, M. E., de Vries, M., Bunet, R., Kitani, S., Nihira, T. and Takano, E.
  • Journal Title: Butyrolactone-Specific Reporter System. Chemistry & Biology Volume: 16 Pages: 951-60
• [Journal Article] Identification of mokB involved in monacolin K biosynthesis in Monascus pilosus (2009)
  • Author(s): Sakai, K., Kinoshita, H. and Nihira, T.
  • Journal Title: Biotechnol. Lett. Volume: 31 Pages: 1911-6
• [Journal Article] Improvement of ML-236B production by genetic engineering in ML-236B high-producing Penicillium citrinum (2009)
  • Author(s): Baba S, Abe Y, Suzuki T, Ono C, Iwamoto K, Nihira T, Hosobuchi M.
  • Journal Title: Appl Microbiol Biotechnol Volume: 83 Pages: 697-704
• [Journal Article] MlcR, a zinc cluster activator protein, is able to bind to a single(A/ T) CGG site of cognate asymmetric motifs in the ML-236B(compactin) biosynthetic gene cluster (2009)
  • Author(s): Baba S, Kinoshita H, Hosobuchi M, and Nihira T.
  • Journal Title: Mol Genet Genomics Volume: 281 Pages: 627-34
• [Journal Article] Hierarchical control of virginiamycin production in Streptomyces virginiae by three pathway-specific regulators : VmsS, VmsT, and VmsR (2009)
  • Author(s): Pulsawat, N., Kitani, S., Fukushima, E., and Nihira, T.
  • Journal Title: Microbiol Volume: 155 Pages: 1250-9
• [Presentation] 放線菌Streptomyces avermitilisにおけるDeoR型転写制御因子の機能解析 (2012)
  • Author(s): Ulanova D、木谷茂、仁平卓也
  • Organizer: 2012農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] 放線菌Streptomyces avermitilisの抗生物質生産を誘発する新型放線菌ホルモン (2012)
  • Author(s): 木谷茂、宮本聖子、高松智、Herawati E、内田美帆、長光亨、池田治生、仁平卓也
  • Organizer: 2012農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] Streptomyces avermitilisにおける放線菌ホルモン受容体様タンパク質AvaL1による二次代謝産物生合成遺伝子群の転写制御 (2012)
  • Author(s): 宮本聖子、木谷茂、池田治生、仁平卓也
  • Organizer: 2012農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] 放線菌Streptomyces lavendulae FRI-5におけるSARP型制御因子の二次代謝における役割 (2012)
  • Author(s): KURNIAWAN YN, 木谷茂、前田亜紗、仁平卓也
  • Organizer: 2012農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] 抗生物質バージニアマイシンS基質供給遺伝子の機能解析 (2012)
  • Author(s): NINGSIH F、木谷茂、福島絵里子、仁平卓也
  • Organizer: 2012農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] A novel Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis (2011)
  • Author(s): 木谷茂、宮本聖子、高松智、長光亨、池田治生、仁平卓也
  • Organizer: The 16th International Symposium on the Biology of Actinomycetes
  • Place of Presentation: Puerto Vallarta, Mexico
  • Year and Date: 2011-12-12
• [Presentation] laeA異種発現によるCordyceps militarisの二次代謝活性化 (2011)
  • Author(s): 木下浩, Rina Rachmawati, 井原史雄, 仁平卓也
  • Organizer: 第11回糸状菌分子生物学コンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2011-11-17
• [Presentation] 昆虫病原性糸状菌Lecanicillium sp.における宿主ベクター系の構築およびku80遺伝子の破壊 (2011)
  • Author(s): 石堂圭一, 木下浩, 井原史雄, 仁平卓也
  • Organizer: 日本生物工学会2011年度大会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-27
• [Presentation] 抗生物質生産と菌糸形態を制御するオートレギュレーターリセプターAvaR3の機能解析: 2011放線菌学会 (2011)
  • Author(s): 宮本聖子、木谷茂、小松護、池田治生、仁平卓也
  • Organizer: 2011 International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-08
• [Presentation] Characterization of ksbC, aγ-butyrolactone-autoregulator receptor gene homolog in Kitasatospora setae : NBRC 14216 : 2011放線菌学会 (2011)
  • Author(s): Aroonsri A、木谷茂、池田治生、仁平卓也
  • Organizer: 2011 International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-08
• [Presentation] dentification of a Philippine Streptomyces isolate and its bioactive compound against methicillin-resistant Staphylococcus aureus : 2011放線菌学会 (2011)
  • Author(s): Zulaybar TO, Papa IA, Perez MTM, Marfori EC, Alcantara EA, Roxas PAT, Nihira T, and Kitani S.
  • Organizer: 2011International union of microbiological societies 2011 congress
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-08
• [Presentation] Analysis of DeoR-family transcriptional regulators in Streptomyces avermitilis : 2011放線菌学会 (2011)
  • Author(s): Ulanova D、木谷茂、仁平卓也
  • Organizer: 2011International union of microbiological societies 2011 congress
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-08
• [Presentation] 抗生物質バージニアマイシンSの基質供給遺伝子の機能解析 (2011)
  • Author(s): NINGSIH F、木谷茂、福島絵里子、仁平卓也
  • Organizer: 2011農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2011-03-26
• [Presentation] 昆虫病原性糸状菌Lecanicillium sp.における宿主ベクター系の構築 (2011)
  • Author(s): 石堂圭一, 木下浩, 井原史雄, 仁平卓也
  • Organizer: 日本農芸化学会2011年度大会
  • Place of Presentation: 京都
  • Year and Date: 2011-03-26
• [Presentation] 麹菌Aspergillus oryzaeを宿主とするテレキノンA異種生産系の構築 (2010)
  • Author(s): 木下浩, 酒井香奈絵, 仁平卓也
  • Organizer: 第10回糸状菌分子生物学コンファレンス
  • Place of Presentation: 広島
  • Year and Date: 2010-11-19
• [Presentation] ポスターAntimicrobial and antioomycete activities of the novel antibiotic farinomalein (2010)
  • Author(s): Sastia PRAMA PUTRI, Hiroshi KINOSHITA, Masayasu KATO, Takuya NIHIRA
  • Organizer: 日本生物工学会2010年度大会
  • Place of Presentation: 宮崎
  • Year and Date: 2010-10-28
• [Presentation] ポスターNew chromone derivative produced by endophytic fungus Daldinia sp. MU41 isolated from Thai medicinal plant Tinospora crispa (2010)
  • Author(s): Ratklao SIRIWACH, Hiroshi KINOSHITA, Kanoktip PANSUKSAN, Watanalai PANBANGRED, Yasuhiro IGARASHI, Takuya NIHIRA
  • Organizer: 日本生物工学会2010年度大会
  • Place of Presentation: 宮崎
  • Year and Date: 2010-10-28
• [Presentation] 「伝統的発酵微生物の新しい利用展開」糸状菌休眠遺伝子群の有効利用 (2010)
  • Author(s): 仁平卓也, 木下浩
  • Organizer: 日本生物工学会2010年度大会
  • Place of Presentation: 宮崎
  • Year and Date: 2010-10-27
• [Presentation] visGの遺伝子機能は抗生物質バージニアマイシンSの基質供給に必須である (2010)
  • Author(s): NINGSIH F、木谷茂、福島絵里子、仁平卓也
  • Organizer: 2010放線菌学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-02
• [Presentation] Metarhizium anisopliaeにおけるヘルボル酸生合成に必須なゲラニルゲラニル二リン酸生合成酵素遺伝子の同定 (2010)
  • Author(s): 木下浩、Singkarabanit Suthitar、井原史雄、仁平卓也
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-29
• [Presentation] タイ土壌由来Streptomyces属放線菌の生産する新規α-ピロン類の構造決定 (2010)
  • Author(s): 嶋崎良子、Watanalai Panbangred、Jirayut Euanorasetr、木谷茂、仁平卓也、福田隆雄、奥直也、五十嵐康弘
  • Organizer: 2010農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] タイ王国土壌由来の放線菌が生産する新規化合物SBI108B1の単離と構造解析 (2010)
  • Author(s): 冨尾紋子、木谷茂、Akkaraphol Srichaisupakit、Bangornsiri Intra、Watanalai Panbangred、福田隆雄、五十嵐康弘、仁平卓也
  • Organizer: 2010農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] タイ王国由来薬用植物に内生する放線菌からのStreptotenol C新規誘導体の単離 (2010)
  • Author(s): Ratama Daduang、木谷茂、Su-Jin Kang、Arinthip Thamchaipenet、福田隆雄、五十嵐康弘、仁平卓也
  • Organizer: 2010農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] 放線菌Streptomyces lavendulae FRI-5におけるオートレギュレーター支配下遺伝子farR2の機能解析 (2010)
  • Author(s): 前田亜紗、木谷茂、飯田彩、Jelger Lycklama、仁平卓也
  • Organizer: 2010農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] 昆虫病原性糸状菌Verticillium lecaniiが生産する環状リポペプチド新規類縁体の単離及び構造解析 (2010)
  • Author(s): 石堂圭一、五十嵐康弘、木下浩、井原史雄、仁平卓也
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] Identification of a novel bioactive compound produced by endophytic fungi isolated from Thai medicinal plant. (2010)
  • Author(s): Ratklao SIRIWACH, Hiroshi KINOSHITA, Kanoktip PANSUKSAN, Watanalai PANBANGRED, Yasuhiro IGARASHI, Takuya NIHIRA
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] Isolation of a new tetramic acid derivative, ophiosetin from the entomopathogenic fungus Elaphocordyceps ophioglossoides by chemical screening. (2010)
  • Author(s): Prama PUTRI Sastia, Hiroshi KINOSHITA, Fumio IHARA, Yasuhiro IGARASHI, Takuya NIHIRA
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] Monacolin K生合成におけるZn(II) 2Cys6タイプ転写制御因子MokHの機能解析 (2009)
  • Author(s): 酒井香奈江, 木下浩, 仁平卓也
  • Organizer: 第9回糸状菌分子生物学コンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2009-11-19
• [Presentation] Isolation of novel bioactive compounds from entomopathogenic fungi by chemical screening : Sastia Prama PUTRI (2009)
  • Author(s): Hiroshi KINOSHITA, F IHARA, Yasuhiro IGARASHI, Takuya NIHIRA
  • Organizer: 第9回糸状菌分子生物学コンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2009-11-18
• [Presentation] 遺伝子工学的手法による昆虫病原性糸状菌の二次代謝活性化 (2009)
  • Author(s): 森椙愛子, 小川孝, 木下浩, 仁平卓也
  • Organizer: 第61回日本生物工学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-24
• [Presentation] Autoregulator-signalling cascades in Streptomyces avermitilis (2009)
  • Author(s): 宮本聖子、春名謙一郎、木谷茂、池田治生、仁平卓也
  • Organizer: 15th International Symposium on the Biology of Actinomycetes
  • Place of Presentation: Shanghai, China
  • Year and Date: 2009-08-22
• [Presentation] Utilization of entomopathogenic fungi for the control of plant pathogenic oomycetes (2009)
  • Author(s): Sastia Prama Putri, Hiroshi Kinoshita, Fumio Ihara, Yasuhiro Igarashi, Takuya Nihira
  • Organizer: 42nd annual meeting of the Society of Invertebrate Pathology(SIP)
  • Place of Presentation: Utha
  • Year and Date: 2009-08-19
• [Presentation] Streptomyces avermitilisのオートレギュレーター制御系におけるAvaR1被制御遺伝子の探索 (2009)
  • Author(s): 宮本聖子、木谷茂、井口博之、池田治生、仁平卓也
  • Organizer: 2009放線菌学会
  • Place of Presentation: 秋田
  • Year and Date: 2009-07-16
• [Presentation] Streptomyces avermitilisにおけるオートレギュレーターレセプタータンパク質AvaL1の機能解析 (2009)
  • Author(s): 春名謙一郎、宮本聖子、木谷茂、池田治生、仁平卓也
  • Organizer: 2009放線菌学会
  • Place of Presentation: 秋田
  • Year and Date: 2009-07-16
• [Presentation] 熱帯域放線菌からの新規生理活性物質探索(1) (2009)
  • Author(s): 千林凱、Watanalai Panbangred、Idsada Lengvehasatit、池田恵、及川勉、木谷茂、仁平卓也、五十嵐康弘
  • Organizer: 2009放線菌学会
  • Place of Presentation: 秋田
  • Year and Date: 2009-07-16
• [Remarks] ホームページ
  • URL: http://www.icb.osaka-u.ac.jp/index.html
• [Remarks]
  • URL: http://www.nihiralab.sakura.ne.jp/index.html