Research activity information

• Mar. 2023 日本農芸化学会, 日本農芸化学会2023年度広島大会（第13回）トピックス賞, 放線菌におけるヒ素二次代謝経路に関する研究


• Mar. 2022 JSBBA, Hot Topics Award (12th) at Annual Meeting of JSBBA 2022, Biological significance of the phage tail-like nanostructures produced by soil bacteria.


• Mar. 2021 JSBBA, Hot Topics Award (11th) at Annual Meeting of JSBBA 2021, Analysis of fatty acyl chain biosynthesis in goadvionins.


• Mar. 2018 JSBBA, Hot Topics Award (9th) at Annual Meeting of JSBBA 2018, Analysis of lanthipeptide biosynthetic enzymes responsible for formation of novel labionen structure.


• Sep. 2016 The Society for Actinomycetes Japan, Hamada award, 放線菌の窒素含有天然物生合成に関する研究


• Mar. 2016 Japan Society for Bioscience, Biotechnology, and Agrochemistry, JSBBA Award for Young Scientists, 放線菌由来窒素含有天然生物活性物質の生合成に関する研究

• Biosynthetic Incorporation of Non-native Aryl Acid Building Blocks into Peptide Products Using Engineered Adenylation Domains.

  Fumihiro Ishikawa, Maya Nohara, Akimasa Miyanaga, Satoki Kuramoto, Natsuki Miyano, Shumpei Asamizu, Fumitaka Kudo, Hiroyasu Onaka, Tadashi Eguchi, Genzoh Tanabe

  Nonribosomal peptides (NRPs), one of the most widespread secondary metabolites in nature, with therapeutically significant activities, are biosynthesized by modular nonribosomal peptide synthetases (NRPSs). Aryl acids contribute to the structural diversity of NRPs as well as nonproteinogenic amino acids and keto acids. We previously confirmed that a single Asn-to-Gly substitution in the 2,3-dihydroxybenzoic acid-activating adenylation (A) domain EntE involved in enterobactin biosynthesis accepts monosubstituted benzoic acid derivatives with nitro, cyano, bromo, and iodo functionalities at the 2 or 3 positions. Here, we showed that the mutant EntE (N235G) accommodates various disubstituted benzoic acid derivatives with halogen, methyl, methoxy, nitro, and cyano functionalities at the 2 and 3 positions and monosubstituted benzoic acid with an alkyne at the 3 position. Structural analysis of the mutant EntE (N235G) with nonhydrolyzable aryl-AMP analogues using 3-chloro-2-methylbenzoic acid and 3-prop-2-ynoxybenzoic acid revealed how bulky 3-chloro-2-methylbenzoic acid and clickable 3-prop-2-ynoxybenzoic acid are recognized by enlarging the substrate-binding pocket of the enzyme. When engineered EntE mutants were coupled with enterobactin and vibriobactin biosynthetic enzymes, 3-hydroxybenzoic acid-, salicylic acid-, and 3-bromo-2-fluorobenzoic acid-containing peptides were produced as early stage intermediates, highlighting the potential of NRP biosynthetic pathway engineering for constructing diverse aryl acid-containing metabolites.

  Dec. 2024, ACS chemical biology, English, International magazine

  [Refereed]

  Scientific journal


• Transcriptionally induced nucleoid-associated protein-like ccr1 in combined-culture serves as a global effector of Streptomyces secondary metabolism.

  Yukun Lei, Hiroyasu Onaka, Shumpei Asamizu

  Combined-cultures involving mycolic acid-containing bacteria (MACB) can stimulate secondary metabolite (SM) production in actinomycetes. In a prior investigation, we screened Streptomyces coelicolor JCM4020 mutants with diminished production of SMs, specifically undecylprodigiosin (RED), which was enhanced by introducing the MACB Tsukamurella pulmonis TP-B0596. In this study, we conducted mutational analysis that pinpointed the sco1842 gene, which we assigned the gene name ccr1 (combined-culture related regulatory protein no. 1), as a crucial factor in the deficient phenotype observed in the production of various major SMs in S. coelicolor A3(2). Notably, the Ccr1 (SCO1842) homolog was found to be highly conserved throughout the Streptomyces genome. Although Ccr1 lacked conserved motifs, in-depth examination revealed the presence of a helix-turn-helix (HTH) motif in the N-terminal region and a helicase C-terminal domain (HCTD) motif in the C-terminal region in some of its homologs. Ccr1 was predicted to be a nucleoid-associated protein (NAP), and its impact on gene transcription was validated by RNA-seq analysis that revealed genome-wide variations. Furthermore, RT-qPCR demonstrated that ccr1 was transcriptionally activated in combined-culture with T. pulmonis, which indicated that Ccr1 is involved in the response to bacterial interaction. We then investigated Streptomyces nigrescens HEK616 in combined-culture, and the knockout mutant of the ccr1 homolog displayed reduced production of streptoaminals and 5aTHQs. This finding reveals that the Ccr1 homolog in Streptomyces species is associated with SM production. Our study elucidates the existence of a new family of NAP-like proteins that evolved in Streptomyces species and play a pivotal role in SM production.

  Corresponding, Jul. 2024, Frontiers in microbiology, 15, 1422977 - 1422977, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Albumin–ruthenium catalyst conjugate for bio-orthogonal uncaging of alloc group

  Kimberly S. Taylor, Madison M. McMonagle, Schaelee C. Guy, Ariana M. Human-McKinnon, Shumpei Asamizu, Heidi J. Fletcher, Bradley W. Davis, Takashi L. Suyama

  An organo–ruthenium catalyst conjugated to albumin efficiently unmasks an alloc group under physiologically relevant conditions.

  Royal Society of Chemistry (RSC), Apr. 2024, Organic & Biomolecular Chemistry, 22(15) (15), 2992 - 3000, English

  [Refereed]

  Scientific journal


• Insights into Arsenic Secondary Metabolism in Actinomycetes from the Structure and Biosynthesis of Bisenarsan

  Shotaro Hoshino, Shinta Ijichi, Shumpei Asamizu, Hiroyasu Onaka

  American Chemical Society (ACS), Aug. 2023, Journal of the American Chemical Society, 145(32) (32), 17863 - 17871, English

  [Refereed]

  Scientific journal


• Biosynthetic diversification of non-ribosomal peptides through activity-based protein profiling of adenylation domains

  Fumihiro Ishikawa, Natsumi Tsukumo, Erika Morishita, Shumpei Asamizu, Saaya Kusuhara, Shinsuke Marumoto, Katsuki Takashima, Hiroyasu Onaka, Genzoh Tanabe

  Coupled with precursor-directed biosynthesis, activity-based protein profiling of non-ribosomal peptide synthetases provides rational guidance for the biosynthetic diversification of non-ribosomal peptides.

  Royal Society of Chemistry (RSC), Aug. 2023, Chemical Communications, 59(62) (62), 9473 - 9476, English

  [Refereed]

  Scientific journal


• Intracellular Phage Tail-Like Nanostructures Affect Susceptibility of Streptomyces lividans to Osmotic Stress

  Toshiki Nagakubo, Shumpei Asamizu, Tatsuya Yamamoto, Manami Kato, Tatsuya Nishiyama, Masanori Toyofuku, Nobuhiko Nomura, Hiroyasu Onaka

  Contractile injection systems (CISs) are a large group of phage tail-like nanostructures conserved among bacteria. Despite their wide distribution, the biological significance of CISs in bacteria remains largely unclear except for a few unicellular bacteria. Here, we show that Streptomyces lividans-a model organism of filamentous Gram-positive bacteria with highly conserved CIS-related gene clusters-produces intracellular CIS-like nanostructures (Streptomyces phage tail-like particles [SLPs]) that affect phenotypes of this bacterium under hyperosmotic conditions. In contrast to typical CISs released from the cells, SLPs are localized in the cytoplasm of S. lividans. In addition, loss of SLPs leads to (i) delayed erection of aerial mycelia on hyperosmotic solid medium and (ii) decreased growth during the transition from exponential growth phase to stationary phase in hyperosmotic liquid medium. Localization of fluorescent protein-tagged SLPs showed partial correlation with cell wall synthesis-related proteins, including MreB, an actin-like cytoskeleton protein. Our pulldown assay and subsequent quantitative proteome analysis also suggest that 30S ribosomal proteins and cell wall-related proteins, including MreB, are coeluted with SLPs. Furthermore, an interaction assay using the recombinant proteins revealed a direct interaction between a sheath protein of SLP and ribosomal protein S16. Results of cross-linking experiments show indirect interactions between SLPs and translation elongation factors. These findings collectively suggest that SLPs are directly or indirectly associated with a protein interaction network within the cytoplasm of S. lividans and that SLP loss ultimately affects the susceptibility of the bacterium to certain stress conditions. IMPORTANCE Recent bioinformatic analyses have revealed that CIS-related gene clusters are highly conserved in Gram-positive actinomycetes, especially members of the genus Streptomyces known for their ability to produce therapeutic antibiotics. While typical CISs are released from the cells and can act as protein translocation systems that inject effector proteins into the target cells, our results indicate the unique intracellular localization of SLPs, CIS-related nanostructures produced by S. lividans. In addition, the direct and indirect interactions of SLPs with cytoplasmic proteins and SLP localization within specific regions of mycelia suggest that the biological significance of SLPs is related to intracellular processes. Further, SLP loss leads to increased susceptibility of S. lividans to osmotic stress, suggesting that production of these phage tail-like nanostructures ultimately affects the fitness of the bacterium under certain stress conditions. This work will provide new insight into the phage tail-like nanostructures highly conserved in Streptomyces species.

  Jun. 2023, mSphere, 8(3) (3), e0011423, English, International magazine

  [Refereed]

  Scientific journal


• SolS-catalyzed sulfoxidation of labionin to solabionin drives antibacterial activity of solabiomycins

  Shinta Ijichi, Shotaro Hoshino, Shumpei Asamizu, Hiroyasu Onaka

  Ribosomally synthesized and posttranslationally modified peptides (RiPPs) with polar-functionalized fatty acyl groups are newly found lipopeptide-class natural products. We recently employed a combined approach of genome mining and stable isotope labeling and discovered solabiomycins as one of the polar-functionalized fatty-acylated RiPPs (PFARs) from Streptomyces lydicus NBRC13058. The solabiomycins contained a characteristic sulfoxide group in the labionin moiety referred to as the 'solabionin' structure for the RiPP moiety. A previous gene knockout experiment indicated that solS, which encodes a putative flavin adenine dinucleotide (FAD)-nicotinamide adenine dinucleotide (phosphate) (NAD(P))-binding protein, is involved in the sulfoxidation of an alkyl sulfide in the solabionin. In this study, we isolated deoxysolabiomycins A and B from ΔsolS mutant and fully determined the chemical structures using a series of NMR experiments. We also tested the bioactivity of deoxysolabiomycins against Gram-positive bacteria, including Mycolicibacterium smegmatis, and notably found that the sulfoxide is critical for the antibacterial activity. To characterize the catalytic activity of SolS, the recombinant protein was incubated with a putative substrate, deoxysolabiomycins, and the cofactors FAD and NADPH. In vitro reactions demonstrated that SolS catalyzes the sulfoxidation, converting deoxysolabiomycins to solabiomycins.

  Corresponding, Jun. 2023, Bioorganic & Medicinal Chemistry Letters, 89, 129323, English, International magazine

  [Refereed]

  Scientific journal


• Regulation of Multidrug Efflux Pumps by TetR Family Transcriptional Repressor Negatively Affects Secondary Metabolism in Streptomyces coelicolor A3(2)

  Yukun Lei, Shumpei Asamizu, Takumi Ishizuka, Hiroyasu Onaka

  Streptomyces spp. are well-known producers of bioactive secondary metabolites (SMs) that serve as pharmaceutical agents. In addition to their ability to produce SMs, Streptomyces spp. have evolved diverse membrane transport systems to protect cells against antibiotics produced by itself or other microorganisms. We previously screened mutants of Streptomyces coelicolor that show a phenotype of reduced undecylprodigiosin (RED) production in a combined-culture with Tsukamurella pulmonis. Here, we identified a point mutation, which reduced RED production, by performing genome resequencing and genetic complementation. We found that inactivation of the sco1718 gene encoding the TetR family transcriptional regulator (TFR) produced a deficient phenotype for several SMs in Streptomyces coelicolor A3(2). In the genome of S. coelicolor A3(2), two other sets of TFR and two-component ATP-binding cassette (ABC) transporter genes (sco4358-4360 and sco5384-5382) were found which had similar effects on the phenotype for both secondary metabolism and antibiotic resistance. An electrophoretic mobility shift assay and quantitative reverse transcription-PCR experiments demonstrated that TFRs repressed the expression of each adjacent two-component ABC transporter genes by binding to the operator sequence. Notably, the Δsco1718 mutant showed increased resistance to several antibiotics of other actinomycete origin. Our results imply the switching of cell metabolism to direct offense (antibiotic production) or defense (efflux pump activation) using costly and limited quantities of cell energy sources (e.g., ATP) in the soil ecosystem. IMPORTANCE The bacterial metabolic potential to synthesize diverse secondary metabolites in the environment has been revealed by recent (meta)genomics of both unculturable and culturable bacteria. These studies imply that bacteria are continuously exposed to harmful chemical compounds in the environment. Streptomyces spp. contain antibiotic efflux pumps and SM biosynthetic gene clusters. However, the mechanism by which soil bacteria, including Streptomyces, survive against toxic compounds in the environment remains unclear. Here, we identified three sets of TFR-ABC transporter genes in Streptomyces coelicolor A3(2). We found that each TFR controlled the expression of respective ABC transporter, and the expression of all ABC transporters negatively impacted SM production and increased antibiotic resistance. Notably, bioinformatic analysis indicated that these TFR-ABC transporter gene sets are highly conserved and widely distributed in the genome of Streptomyces species, indicating the importance of systematic regulation that directs antibiotic production and xenobiotic excretion.

  Corresponding, May 2023, Applied and Environmental Microbiology, 89(3) (3), e0182222, English, International magazine

  [Refereed]

  Scientific journal


• Biochemical Characterization of GacI, a Bifunctional Glycosyltransferase–Phosphatase Enzyme Involved in Acarbose Biosynthesis in Streptomyces glaucescens GLA.O

  Takeshi Tsunoda, Shumpei Asamizu, Taifo Mahmud

  Acarbose, a pseudotetrasaccharide produced by several strains of Actinoplanes and Streptomyces, is an α-glucosidase inhibitor clinically used to control type II diabetes. Bioinformatic analysis of the biosynthetic gene clusters of acarbose in Actinoplanes sp. SE50/110 (the acb cluster) and Streptomyces glaucescens GLA.O (the gac cluster) revealed their distinct genetic organizations and presumably biosynthetic pathways. However, to date, only the acarbose pathway in the SE50/110 strain has been extensively studied. Here, we report that GacI, one of the proteins that appear to be different between the two pathways, is a bifunctional glycosyltransferase family 5 (GT5)-phosphatase (PP) enzyme that functions at two different steps in acarbose biosynthesis in S. glaucescens GLA.O. In the acb pathway, the GT and the PP reactions are performed by two different enzymes. Truncated GacI proteins having only the GT or the PP domain showed comparable catalytic activity with the full-length GacI, indicating that domain separation does not significantly affect their respective catalytic activity. GacI, which is widely distributed in many Streptomyces, represents the first example of naturally occurring GT5-PP bifunctional enzymes biochemically characterized.

  American Chemical Society (ACS), Nov. 2022, Biochemistry, 61(22) (22), 2628 - 2635, English, International magazine

  [Refereed]

  Scientific journal


• Stable Isotope-Guided Metabolomics Reveals Polar-Functionalized Fatty-Acylated RiPPs from Streptomyces

  Shumpei Asamizu, Shinta Ijichi, Shotaro Hoshino, Hansaem Jo, Hidenori Takahashi, Yuko Itoh, Sohkichi Matsumoto, Hiroyasu Onaka

  Ribosomally synthesized and posttranslationally modified peptides (RiPPs) with polar-functionalized fatty acyl groups are a rarely found untapped class of natural products. Although polar-functionalized fatty-acylated RiPPs (PFARs) have potential as antimicrobial agents, the repertoire is still limited. Therefore, expanding the chemical space is expected to contribute to the development of pharmaceutical agents. In this study, we performed genome mining and stable isotope-guided comparative metabolomics to discover new PFAR natural products. We focused on the feature that PFARs incorporate l-arginine or l-lysine as the starter unit of the fatty acyl group and fed 13C6,15N4-l-arginine or 13C6,15N2-l-lysine to bacterial cultures. Metabolites were extracted and compared with those extracted from nonlabeled l-arginine or l-lysine fed cultures. We identified putative PFARs and successfully isolated solabiomycin A and B from Streptomyces lydicus NBRC 13 058 and albopeptin B from Streptomyces nigrescens HEK616, which contained a sulfoxide group in the labionin moiety. The gene disruption experiment indicated that solS, which encodes a putative flavin adenine dinucleotide (FAD)-nicotinamide adenine dinucleotide (phosphate) (NAD(P))-binding protein, is involved in the sulfoxidation of aryl sulfides. The solabiomycins showed antibacterial activity against Gram-positive bacteria, including Mycobacterium tuberculosis H37Rv with a minimum 95% inhibitory concentration (MIC95) of 3.125 μg/mL, suggesting their potential as antituberculosis agents.

  American Chemical Society (ACS), Oct. 2022, ACS Chemical Biology, 17(10) (10), 2936 - 2944, English, International magazine

  [Refereed]

  Scientific journal


• Comparative Metabolomics Reveals a Bifunctional Antibacterial Conjugate from Combined-Culture of Streptomyces hygroscopicus HOK021 and Tsukamurella pulmonis TP-B0596

  Shumpei Asamizu, Abrory Agus Cahya Pramana, Sung-Jin Kawai, Yoshichika Arakawa, Hiroyasu Onaka

  To investigate the potential for secondary metabolite biosynthesis by Streptomyces species, we employed a coculture method to discover natural bioactive products and identified specific antibacterial activity from a combined-culture of Streptomyces hygroscopicus HOK021 and Tsukamurella pulmonis TP-B0596. Molecular networking using ultrahigh performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) data revealed a specific clade of metabolites in this combined-culture that were not detected in both monocultures. Using the chemical profiles, a previously unidentified conjugate between FabF inhibitor and catechol-type siderophore was successfully identified and named harundomycin A. Harundomycin A was a conjugate between the 2,4-dihydroxy-3-aminobenzoate moiety of platensimycin and N,N'-bis(2,3-dihydroxybenzoyl)-O-seryl-cysteine (bisDHBA-Ser-Cys) with a thioester linkage. Along with the production of harundomycin A, platensimycin, its thiocarboxylic acid form thioplatensimycin, enterobactin, and its degradation product N,N'-bis(2,3-dihydroxybenzoyl)-O-l-seryl-dehydroalanine (bisDHBA-Ser-Dha) were also induced in the combined-culture. Genomic data of S. hygroscopicus HOK021 and T. pulmonis TP-B0596 indicated that strain HOK021 possessed biosynthetic gene clusters for both platensimycin and enterobactin, and thereby revealed that T. pulmonis stimulates HOK021 and acts as an inducer of both of these metabolites. Although the harundomycin A was modified by bulky bisDHBA-Ser-Cys, responsible for the binding to the target molecule FabF, it showed a similar antibacterial spectrum to platensimycin, including against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, suggesting that the pharmacophore is platensimycin. Additionally, Chrome Azurol S assay showed that harundomycin A possesses ferric iron-chelating activity comparable to that of enterobactin. Our study demonstrated the transformation of existing natural products to bifunctional molecules driven by bacterial interaction.

  American Chemical Society (ACS), Sep. 2022, ACS Chemical Biology, 17(9) (9), 2664 - 2672, English, International magazine

  [Refereed]

  Scientific journal


• Effects of carbon ion beam-induced mutagenesis for the screening of RED production-deficient mutants of Streptomyces coelicolor JCM4020

  Masaomi Yanagisawa, Shumpei Asamizu, Katsuya Satoh, Yutaka Oono, Hiroyasu Onaka

  Jul. 2022, PLoS One, 17(7) (7), e0270379, English, International magazine

  [Refereed]

  Scientific journal


• Intimate relationships among actinomycetes and mycolic acid-containing bacteria

  Manami Kato, Shumpei Asamizu, Hiroyasu Onaka

  Springer Science and Business Media LLC, May 2022, Scientific Reports, 12(1) (1), 7222, English, International magazine

  [Refereed]

  Scientific journal


• Kimidinomycin, a new antibiotic against Mycobacterium avium complex, produced by Streptomyces sp. KKTA-0263

  Ayumi Hikima, Shumpei Asamizu, Hiroyasu Onaka, Huiping Zhang, Hiroshi Tomoda, Nobuhiro Koyama

  Feb. 2022, The Journal of Antibiotics, 75(2) (2), 72 - 76, English, International magazine

  [Refereed]

  Scientific journal


• Differential Biosynthesis and Roles of Two Ferrichrome-Type Siderophores, ASP2397/AS2488053 and Ferricrocin, in Acremonium persicinum

  Yoshiki Asai, Tomoshige Hiratsuka, Miyu Ueda, Yumi Kawamura, Shumpei Asamizu, Hiroyasu Onaka, Manabu Arioka, Shinichi Nishimura, Minoru Yoshida

  Jan. 2022, ACS Chemical Biology, 17(1) (1), 207 - 216, English, International magazine

  [Refereed]

  Scientific journal


• Phage tail-like nanostructures affect microbial interactions between Streptomyces and fungi

  Toshiki Nagakubo, Tatsuya Yamamoto, Shumpei Asamizu, Masanori Toyofuku, Nobuhiko Nomura, Hiroyasu Onaka

  Oct. 2021, Scientific Reports, 11(1) (1), 20116, English, International magazine

  [Refereed]

  Scientific journal


• Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides

  Ryosuke Kozakai, Takuto Ono, Shotaro Hoshino, Hidenori Takahashi, Yohei Katsuyama, Yoshinori Sugai, Taro Ozaki, Kazuya Teramoto, Kanae Teramoto, Koichi Tanaka, Ikuro Abe, Shumpei Asamizu, Hiroyasu Onaka

  Sep. 2020, Nature chemistry, 12(9) (9), 869 - 877, English, International magazine

  [Refereed]

  Scientific journal


• Minimal lactazole scaffold for in vitro thiopeptide bioengineering

  Alexander A Vinogradov, Morito Shimomura, Yuki Goto, Taro Ozaki, Shumpei Asamizu, Yoshinori Sugai, Hiroaki Suga, Hiroyasu Onaka

  May 2020, Nature communications, 11(1) (1), 2272, English, International magazine

  [Refereed]

  Scientific journal


• Bioactive properties of streptomyces may affect the dominance of Tricholoma matsutake in shiro

  Lu-Min Vaario, Shumpei Asamizu, Tytti Sarjala, Norihisa Matsushita, Hiroyasu Onaka, Yan Xia, Hiroyuki Kurokochi, Shin-Ichi Morinaga, Jian Huang, Shijie Zhang, Chunlan Lian

  Apr. 2020, Symbiosis, 81, 1 - 13, English

  [Refereed]

  Scientific journal


• Chemical Interactions of Cryptic Actinomycete Metabolite 5-Alkyl-1,2,3,4-tetrahydroquinolines through Aggregate Formation

  Ryosuke Sugiyama, Takahiro Nakatani, Shinichi Nishimura, Kei Takenaka, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya

  Sep. 2019, Angewandte Chemie (International ed. in English), 58(38) (38), 13486 - 13491, English, International magazine

  [Refereed]

  Scientific journal


• Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines

  Taro Ozaki, Ryosuke Sugiyama, Morito Shimomura, Shinichi Nishimura, Shumpei Asamizu, Yohei Katsuyama, Hideaki Kakeya, Hiroyasu Onaka

  Feb. 2019, Organic & biomolecular chemistry, 17(9) (9), 2370 - 2378, English, International magazine

  [Refereed]

  Scientific journal


• Characterization of a wild Sake-brewing yeast isolated from barley malt in Toyama

  ONAKA Hiroyasu, MARUYAMA Jun-ichi, ASAMIZU Shumpei, KUROIWA Mayumi, KITAMOTO Katsuhiko, YAMADA Masato, GOSHIMA Tetsuya, AKAO Takeshi

  A wild sake-brewing yeast, Toyama yeast（Toyama-Umare-no-Koubo）was isolated from the malt of six-rowed barley harvested in Takaoka, Toyama. Molecular phylogenetic analysis revealed that Toyama yeast had the highest homology with Saccharomyces cerevisiae NBRC2114（Kotobukiya whisky No. 1）in the internal transcribed spacers（ITS）region. A small-scale sake brewing test revealed that the mash（moromi）fermentation period for Toyama yeast was 3 days longer than that for K701 yeast, and the alcohol concentration reached almost the same value i.e. 18%. In the composition of organic acids in sake fermented by Toyama yeast, the amounts of acetic acid, malic acid, and succinic acid were considerably different from sake fermented by K701. Considering volatile contents, sake fermented by Toyama yeast also contained more higher-alcohols and fewer esters than K701 sake. In amino acid content, sake fermented by Toyama yeast was much higher than K701. These properties also appeared in organoleptic evaluation. Further, Toyama yeast sake has unique and distinctive properties characterized by differences in aroma and flavor such an acidic smell, umami, heaviness, zatsumi, and weakness as compared to K701 sake. Commercialized brewing with Toyama yeast has been done five times in Narimasa Shuzo Breweries; the current brewing sake has become rich in flavor and has a sharp finish. Also, since this yeast is not a sake yeast but a wild yeast, it has been also used for the brewing of craft beer, wine, and whiskey.

  Brewing Society of Japan, 2019, JOURNAL OF THE BREWING SOCIETY OF JAPAN, 114(10) (10), 645 - 653, Japanese


• Umezawamides, new bioactive polycyclic tetramate macrolactams isolated from a combined-culture of Umezawaea sp. and mycolic acid-containing bacterium

  Shotaro Hoshino, Chin Piow Wong, Masahiro Ozeki, Huiping Zhang, Fumiaki Hayashi, Takayoshi Awakawa, Shumpei Asamizu, Hiroyasu Onaka, Ikuro Abe

  Jul. 2018, The Journal of Antibiotics, 71(7) (7), 653 - 657, English, International magazine

  [Refereed]

  Scientific journal


• Mycolic Acid Containing Bacterium Stimulates Tandem Cyclization of Polyene Macrolactam in a Lake Sediment Derived Rare Actinomycete

  Shotaro Hoshino, Masahiro Okada, Takayoshi Awakawa, Shumpei Asamizu, Hiroyasu Onaka, Ikuro Abe

  Sep. 2017, Organic letters, 19(18) (18), 4992 - 4995, English, International magazine

  [Refereed]

  Scientific journal


• Evolution and Distribution of C7-Cyclitol Synthases in Prokaryotes and Eukaryotes

  Andrew R Osborn, Kelsey M Kean, Khaled M Alseud, Khaled H Almabruk, Shumpei Asamizu, Janet A Lee, P Andrew Karplus, Taifo Mahmud

  Apr. 2017, ACS chemical biology, 12(4) (4), 979 - 988, English, International magazine

  [Refereed]

  Scientific journal


• Dissection of goadsporin biosynthesis by in vitro reconstitution leading to designer analogues expressed in vivo

  Taro Ozaki, Kona Yamashita, Yuki Goto, Morito Shimomura, Shohei Hayashi, Shumpei Asamizu, Yoshinori Sugai, Haruo Ikeda, Hiroaki Suga, Hiroyasu Onaka

  Feb. 2017, Nature communications, 8, 14207, English, International magazine

  [Refereed]

  Scientific journal


• Discovery and Total Synthesis of Streptoaminals: Antimicrobial [5,5]-Spirohemiaminals from the Combined-Culture of Streptomyces nigrescens and Tsukamurella pulmonis

  Ryosuke Sugiyama, Shinichi Nishimura, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya

  Aug. 2016, Angewandte Chemie (International ed. in English), 55(35) (35), 10278 - 10282, English, International magazine

  [Refereed]

  Scientific journal


• Insights into the Biosynthesis of Dehydroalanines in Goadsporin

  Taro Ozaki, Yukari Kurokawa, Shohei Hayashi, Naoya Oku, Shumpei Asamizu, Yasuhiro Igarashi, Hiroyasu Onaka

  Feb. 2016, Chembiochem : a European journal of chemical biology, 17(3) (3), 218 - 223, English, International magazine

  [Refereed]

  Scientific journal


• Killing of Mycolic Acid-Containing Bacteria Aborted Induction of Antibiotic Production by Streptomyces in Combined-Culture

  Shumpei Asamizu, Taro Ozaki, Kanae Teramoto, Katsuya Satoh, Hiroyasu Onaka

  Nov. 2015, PLoS One, 10(11) (11), e0142372, English, International magazine

  [Refereed]

  Scientific journal


• Mycolic acid-containing bacteria activate heterologous secondary metabolite expression in Streptomyces lividans

  Hiroyasu Onaka, Taro Ozaki, Yukiko Mori, Masumi Izawa, Shohei Hayashi, Shumpei Asamizu

  Sep. 2015, The Journal of Antibiotics, 68(9) (9), 594 - 597, English, International magazine

  [Refereed]

  Scientific journal


• De novo synthesis of a sunscreen compound in vertebrates

  Andrew R Osborn, Khaled H Almabruk, Garrett Holzwarth, Shumpei Asamizu, Jane LaDu, Kelsey M Kean, P Andrew Karplus, Robert L Tanguay, Alan T Bakalinsky, Taifo Mahmud

  May 2015, eLife, 4, e05919, English, International magazine

  [Refereed]

  Scientific journal


• 5-Alkyl-1,2,3,4-tetrahydroquinolines, new membrane-interacting lipophilic metabolites produced by combined culture of Streptomyces nigrescens and Tsukamurella pulmonis

  Ryosuke Sugiyama, Shinichi Nishimura, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya

  Apr. 2015, Organic letters, 17(8) (8), 1918 - 1921, English, International magazine

  [Refereed]

  Scientific journal


• Structure of a sedoheptulose 7-phosphate cyclase: ValA from Streptomyces hygroscopicus

  Kelsey M Kean, Sara J Codding, Shumpei Asamizu, Taifo Mahmud, P Andrew Karplus

  Jul. 2014, Biochemistry, 53(26) (26), 4250 - 4260, English, International magazine

  [Refereed]

  Scientific journal


• Genome mining reveals a minimum gene set for the biosynthesis of 32-membered macrocyclic thiopeptides lactazoles

  Shohei Hayashi, Taro Ozaki, Shumpei Asamizu, Haruo Ikeda, Satoshi Ōmura, Naoya Oku, Yasuhiro Igarashi, Hiroshi Tomoda, Hiroyasu Onaka

  May 2014, Chemistry & Biology, 21(5) (5), 679 - 688, English, International magazine

  [Refereed]

  Scientific journal


• Genetic approaches to generate hyper-producing strains of goadsporin: the relationships between productivity and gene duplication in secondary metabolite biosynthesis

  Kentaro Haginaka, Shumpei Asamizu, Taro Ozaki, Yasuhiro Igarashi, Tamotsu Furumai, Hiroyasu Onaka

  Mar. 2014, Bioscience, Biotechnology, and Biochemistry, 78(3) (3), 394 - 399, English, International magazine

  [Refereed]

  Scientific journal


• Comparative metabolomic analysis of an alternative biosynthetic pathway to pseudosugars in Actinosynnema mirum DSM 43827

  Shumpei Asamizu, Mostafa Abugreen, Taifo Mahmud

  Lead, Sep. 2013, Chembiochem : a European journal of chemical biology, 14(13) (13), 1548 - 1551, English, International magazine

  [Refereed]

  Scientific journal


• Coupling reaction of indolepyruvic acid by StaD and its product: implications for biosynthesis of indolocarbazole and violacein

  Shumpei Asamizu, Satoshi Hirano, Hiroyasu Onaka, Hiroyuki Koshino, Yoshitsugu Shiro, Shingo Nagano

  Lead, Nov. 2012, Chembiochem : a European journal of chemical biology, 13(17) (17), 2495 - 2500, English, International magazine

  [Refereed]

  Scientific journal


• The α-ketoglutarate/Fe(II)-dependent dioxygenase VldW is responsible for the formation of validamycin B

  Khaled H Almabruk, Shumpei Asamizu, Ada Chang, Sheril G Varghese, Taifo Mahmud

  Oct. 2012, Chembiochem : a European journal of chemical biology, 13(15) (15), 2209 - 2211, English, International magazine

  [Refereed]

  Scientific journal


• Mechanistic insights into validoxylamine A 7'-phosphate synthesis by VldE using the structure of the entire product complex

  Michael C Cavalier, Young-Sun Yim, Shumpei Asamizu, David Neau, Khaled H Almabruk, Taifo Mahmud, Yong-Hwan Lee

  Sep. 2012, PLoS One, 7(9) (9), e44934, English, International magazine

  [Refereed]

  Scientific journal


• Evolutionary divergence of sedoheptulose 7-phosphate cyclases leads to several distinct cyclic products

  Shumpei Asamizu, Pengfei Xie, Corey J Brumsted, Patricia M Flatt, Taifo Mahmud

  Lead, Jul. 2012, Journal of the American Chemical Society, 134(29) (29), 12219 - 12229, English, International magazine

  [Refereed]

  Scientific journal


• Characterization and functional modification of StaC and RebC, which are involved in the pyrrole oxidation of indolocarbazole biosynthesis

  Shumpei Asamizu, Yoshitsugu Shiro, Yasuhiro Igarashi, Shingo Nagano, Hiroyasu Onaka

  Lead, Nov. 2011, Bioscience, Biotechnology, and Biochemistry, 75(11) (11), 2184 - 2193, English, International magazine

  [Refereed]

  Scientific journal


• Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis

  Shumpei Asamizu, Jongtae Yang, Khaled H Almabruk, Taifo Mahmud

  Lead, Aug. 2011, Journal of the American Chemical Society, 133(31) (31), 12124 - 12135, English, International magazine

  [Refereed]

  Scientific journal


• Theoretical and Experimental Studies of the Conversion of Chromopyrrolic Acid to an Antitumor Derivative by Cytochrome P450 StaP: The Catalytic Role of Water Molecules

  Yong Wang, Hui Chen, Masatomo Makino, Yoshitsugu Shiro, Shingo Nagano, Shumpei Asamizu, Hiroyasu Onaka, Sason Shaik

  American Chemical Society (ACS), May 2009, Journal of the American Chemical Society, 131(19) (19), 6748 - 6762, English

  [Refereed]

  Scientific journal


• Crystal Structure of VioE, a Key Player in the Construction of the Molecular Skeleton of Violacein

  Satoshi Hirano, Shumpei Asamizu, Hiroyasu Onaka, Yoshitsugu Shiro, Shingo Nagano

  Lead, Elsevier BV, Mar. 2008, Journal of Biological Chemistry, 283(10) (10), 6459 - 6466, English

  [Refereed]

  Scientific journal


• Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton

  Masatomo Makino, Hiroshi Sugimoto, Yoshitsugu Shiro, Shumpei Asamizu, Hiroyasu Onaka, Shingo Nagano

  Staurosporine isolated from Streptomyces sp. TP-A0274 is a member of the family of indolocarbazole alkaloids that exhibit strong antitumor activity. A key step in staurosporine biosynthesis is the formation of the indolocarbazole core by intramolecular C–C bond formation and oxidative decarboxylation of chromopyrrolic acid (CPA) catalyzed by cytochrome P450 StaP (StaP, CYP245A1). In this study, we report x-ray crystal structures of CPA-bound and -free forms of StaP. Upon substrate binding, StaP adopts a more ordered conformation, and conformational rearrangements of residues in the active site are also observed. Hydrogen-bonding interactions of two carboxyl groups and T-shaped π–π interactions with indole rings hold the substrate in the substrate-binding cavity with a conformation perpendicular to the heme plane. Based on the crystal structure of StaP–CPA complex, we propose that C–C bond formation occurs through an indole cation radical intermediate that is equivalent to cytochrome c peroxidase compound I [Sivaraja M, Goodin DB, Smith M, Hoffman BM (1989) Science 245:738–740]. The subsequent oxidative decarboxylation reaction is also discussed based on the crystal structure. Our crystallographic study shows the first crystal structures of enzymes involved in formation of the indolocarbazole core and provides valuable insights into the process of staurosporine biosynthesis, combinatorial biosynthesis of indolocarbazoles, and the diversity of cytochrome P450 chemistry.

  Proceedings of the National Academy of Sciences, Jul. 2007, Proceedings of the National Academy of Sciences, 104(28) (28), 11591 - 11596, English

  [Refereed]

  Scientific journal


• VioE, a prodeoxyviolacein synthase involved in violacein biosynthesis, is responsible for intramolecular indole rearrangement

  Shumpei Asamizu, Yasuo Kato, Yasuhiro Igarashi, Hiroyasu Onaka

  Lead, Elsevier BV, Apr. 2007, Tetrahedron Letters, 48(16) (16), 2923 - 2926, English

  [Refereed]

  Scientific journal


• Direct formation of chromopyrrolic acid from indole-3-pyruvic acid by StaD, a novel hemoprotein in indolocarbazole biosynthesis

  Shumpei Asamizu, Yasuo Kato, Yasuhiro Igarashi, Tamotsu Furumai, Hiroyasu Onaka

  Lead, Elsevier BV, Jan. 2006, Tetrahedron Letters, 47(4) (4), 473 - 475, English

  [Refereed]

  Scientific journal


• Cytochrome P450 Homolog Is Responsible for C–N Bond Formation between Aglycone and Deoxysugar in the Staurosporine Biosynthesis ofStreptomyces sp. TP-A0274

  Hiroyasu ONAKA, Shumpei ASAMIZU, Yasuhiro IGARASHI, Ryuji YOSHIDA, Tamotsu FURUMAI

  Oxford University Press (OUP), Jan. 2005, Bioscience, Biotechnology, and Biochemistry, 69(9) (9), 1753 - 1759, English

  [Refereed]

  Scientific journal

• Redox-active compound generated by bacterial crosstalk induces hypha branching in Streptomyces species

  Manami Kato, Shumpei Asamizu, Hiroyasu Onaka

  Abstract Chemical cross talks betweenMycolicibacterium septicumHEK138M andBacillus subtilis168 affect the bacterial morphology ofStreptomyces variegatusHEK138A. We found thatS. variegatusexhibits unusual hyphae branching by the bacterial interaction. We aimed to elucidate the mechanism by performing activity guided purification of substances that induce the unusual cell morphology. We found that pyrogallol, a redox active aromatic small molecule induced significant hyphae branching inS. variegatusand the activity was also observed in some of otherStreptomycesspecies. Interestingly, the pyrogallol activity was diminished by adding catalase, which broke down H₂O₂. To further confirm the involvement, H₂O₂was tested and similar activity which induced hyphal branching was observed. This indicates that reactive oxygen species (ROS) generated by redox-active compound (RAC) is the inducing factor of hyphae branching. Further investigation revealed that pyrogallol was generated by NahG enzyme homolog ofM. septicumusing 2,3-dihydroxybenzoic acid as substrate by heterologous expression inE. coli. Moreover, co-culture with gene knock-out mutants revealed that 2,3-dihydroxybenzoic acid was supplied byB. subtilisproduced as intermediate of bacterial siderophore bacillibactin. Since the hyphae branching of vegetative mycelium can increase the density of filamentous network and consequently help secure the milieu in soil, our results suggested that those filamentous soil bacteria use ROS which can be supplied from plant derived RAC as a signal. As those RAC ubiquitously exist in soil environment, the system will be beneficial for sensing the nutrient sources in addition to the generally considered defensive response to oxidative stress. Importance The characterization of interactions between three or more bacteria are lacking as these interactions are visually imperceptible in general. Our current study revealed changes of morphological behavior by the bacterial interaction. This study showed that hydrogen peroxide generated by redox-active compound derived from a breakdown product of siderophore can significantly increase the number of hyphae tip extension in filamentous bacteria. Our result implies the existence of oxidative response system using a low amount of reactive oxygen species as an integrated signal to sense the plant-derived carbon source by the filamentous soil bacteria. As a result of sensing, filamentous soil bacteria may decide whether the hypha tip should be extended to further explore the area or increase the tips to densify filamentous network to monopolize the nutrients in the milieu.

  Corresponding, Cold Spring Harbor Laboratory, 13 Jan. 2023, bioRxiv


• ミコール酸含有細菌の接触刺激による放線菌二次代謝応答機構の変異ゲノム解析を用いた解明

  浅水俊平

  Dec. 2020, Institute for Fermentation, Osaka. Research Communications, (34) (34)


• Combined-culture: Antibiotic Production Induced by Microbial Physical Contact

  尾仲宏康, 浅水俊平

  15 Jun. 2020, Journal of Environmental Biotechnology (Web), 20(1) (1)


• Analysis of lanthipeptide biosynthetic enzymes responsible for formation of novel goadionin structure

  菅井佳宣, 菅井佳宣, 尾崎太郎, 尾崎太郎, 浅水俊平, 尾仲宏康, 菅裕明, 後藤佑樹

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 167 - 177, Japanese


• RNA sequencing analysis of contact-dependent secondary metabolism responses by Streptomyces coelicolor

  浅水俊平, 尾崎太郎, 菅井佳宣, 尾仲宏康, 佐々木槇子, 吉田昭介, 吉田昭介, 宮本憲二

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 87 - 94, Japanese


• Analysis of response deficient mutants of Streptomyces coelicolor generated by heavy ion beam induced mutagenesis to contact-dependent stimuli by Tsukamurella pulmonis

  浅水俊平, 菅井佳宣, 尾崎太郎, 尾仲宏康, 佐藤勝也, 大野豊

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 95 - 104, Japanese


• Goadsporin, a specific inhibitor of actinomycetal signal recognition particle

  尾崎太郎, 尾崎太郎, 菅井佳宜, 浅水俊平, 尾仲宏康

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 129 - 139, Japanese


• Dissection of goadsporin biosynthetic machinery by in vitro reconstitution leading to in vivo production of designer analogues

  尾崎太郎, 尾崎太郎, 菅井佳宣, 浅水俊平, 尾仲宏康, 後藤佑樹, 菅裕明, 池田治生

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 141 - 154, Japanese


• Genome mining reveals a minimum gene set for the biosynthesis of 32-membered macrocyclic thiopeptides lactazoles

  林昌平, 林昌平, 尾崎太郎, 尾崎太郎, 浅水俊平, 尾仲宏康, 大村智, 供田洋, 池田治生, 奥直也, 五十嵐康弘

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 155 - 166, Japanese


• A new sideromycin-like antibiotic from combined-culture of Streptomyces hygroscopicus HOK021 and Tsukamurella pulmonis

  浅水俊平, 菅井佳宣, 尾仲宏康, 河合盛進, 荒川宜親

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 117 - 127, Japanese


• Requirement of live mycolic acid-containing bacteria for induction of antibiotic production by Streptomyces in combined-culture

  浅水俊平, 尾崎太郎, 尾仲宏康, 佐藤勝也, 寺本華奈江, 寺本華奈江

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 73 - 86, Japanese


• Studies on the biosynthesis of novel alkaloids derived from the combined-culture of Streptomyces nigrescens HEK616 and Tsukamurella pulmonis

  尾崎太郎, 尾崎太郎, 浅水俊平, 尾仲宏康, 杉山龍介, 西村慎一, 掛谷秀昭

  大阪 : 発酵研究所, 20 Dec. 2018, Institute for Fermentation, Osaka. Research Communications, (32) (32), 105 - 115, Japanese


• トクシュウ ビセイブツ ノ 「 コエ 」 ガ キキタクテ … タンサイボウ セイブツ ノ コミュニケーション スキル

  浅水 俊平, 尾仲 宏康

  コレクション : 国立国会図書館デジタルコレクション > 電子書籍・電子雑誌 > 学術機関 > 学協会

  吹田 : 日本生物工学会, 2018, 生物工学会誌 / 日本生物工学会 編, 96(8) (8), 457 - 460, Japanese


• Biosynthesis of nitrogen-containing natural products, C7N aminocyclitols and bis-indoles, from actinomycetes

  Shumpei Asamizu

  Abstract Actinomycetes are a major source of bioactive natural products with important pharmaceutical properties. Understanding the natural enzymatic assembly of complex small molecules is important for rational metabolic pathway design to produce “artificial” natural products in bacterial cells. This review will highlight current research on the biosynthetic mechanisms of two classes of nitrogen-containing natural products, C7N aminocyclitols and bis-indoles. Validamycin A is a member of C7N aminocyclitol natural products from Streptomyces hygroscopicus. Here, two important biosynthetic steps, pseudoglycosyltranferase-catalyzed C–N bond formation, and C7-sugar phosphate cyclase-catalyzed divergent carbasugar formation, will be reviewed. In addition, the bis-indolic natural products indolocarbazole, staurosporine from Streptomyces sp. TP-A0274, and rearranged bis-indole violacein from Chromobacterium violaceum are reviewed including the oxidative course of the assembly pathway for the bis-indolic scaffold. The identified biosynthesis mechanisms will be useful to generating new biocatalytic tools and bioactive compounds.

  Corresponding, Informa UK Limited, 04 May 2017, Bioscience, Biotechnology, and Biochemistry, 81(5) (5), 871 - 881

  [Refereed][Invited]


• Exploiting the potential of biosynthesis of natural products by actinomycetes: bacterial interaction-driven natural product discovery and biosynthetic machinery

  浅水 俊平

  Corresponding, Jun. 2017, Actinomycetologica, 31(1) (1), S30 - S40

  [Invited]


• もう無視できない天然物資源(バイオミディア)

  浅水,俊平

  日本生物工学会, 25 Aug. 2015, 生物工学会誌 : Seibutsu-kogaku Kaishi, 93(8) (8), 489, Japanese

• Functional analysis of sco1842 gene involved in the pigment production response by combined-cultures

  久保木綾梨, LEI Yukun, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), 2024


• Establishment of unnatural thiopeptide fermentation platform for de novo RiPPs drug discovery

  伊地知新太, 永井栄美子, 浅水俊平, VINOGRADOV Alexander A., 後藤佑樹, 菅裕明, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), 2024


• Identification of a candidate effector protein of intracellular phage tail-like nanostructures

  永久保利紀, 西山辰也, 浅水俊平, 尾仲宏康, 野村暢彦, 豊福雅典

  日本農芸化学会大会講演要旨集(Web), 2024


• In Streptomyces, Involvement of sigR-mediated oxidative stress response in pyrogallol-induced hyphae branching formation

  福原彩穂, 加藤愛美, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), 2024


• Establishment of unnatural cyclic peptide fermentation platform for RiPP drug discovery

  伊地知新太, 永井栄美子, 星野翔太郎, 浅水俊平, VINOGRADOV Alexander A., 後藤佑樹, 後藤佑樹, 菅裕明, 尾仲宏康

  日本生物工学会大会講演要旨集, 2024


• Discovery of phage tail-like nanostructures associated with a host stress response and implication of their ecological impact.

  永久保利紀, 永久保利紀, 西山辰也, 浅水俊平, 浅水俊平, 山本達也, 加藤愛美, 加藤愛美, 野村暢彦, 野村暢彦, 野村暢彦, 豊福雅典, 豊福雅典, 尾仲宏康, 尾仲宏康

  日本微生物生態学会大会(Web), Nov. 2023


• Signals from Nature: The Environmental Response of Actinomycetes via Pyrogallol

  加藤愛美, 加藤愛美, 加藤愛美, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本微生物生態学会大会(Web), Nov. 2023


• Microbial chemical communications drive hyphal branching of actinomycetes

  浅水俊平, 浅水俊平, 加藤愛美, 加藤愛美, 尾仲宏康, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2023


• Exploration of arsenic secondary metabolic pathways distributed in actinomycetes

  星野翔太郎, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2023


• Sulfoxidation of labionin enhances antibacterial activity

  伊地知新太, 星野翔太郎, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2023


• Analysis of a gene involved in secondary metabolism fully conserved in Streptomyces species

  LEI Yukun, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2023


• Analysis of oxidoreductase responsible for the formation of a new solabionin scaffold

  伊地知新太, 星野翔太郎, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2023


• Analysis of phage tail-like nanostructures conserved in Streptomyces bacteria

  永久保利紀, 永久保利紀, 浅水俊平, 浅水俊平, 山本達也, 加藤愛美, 豊福雅典, 豊福雅典, 野村暢彦, 野村暢彦, 尾仲宏康, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2023


• Studies on arsenic-related secondary metabolism in actinobacteria

  星野翔太郎, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2023


• Discovery of actinobacteria drug efflux mechanism mediated by second messenger c-di-GMP

  LEI Yukun, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2022


• Isotope-guided metabolomics reveals polar-functionalized fatty-acylated ribosomally synthesized and posttranslationally modified peptides

  浅水俊平, 星野翔太郎, 伊地知新太, JO Hanseam, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2022


• Studies on organo-arsenic secondary metabolites produced by actinobacteria

  星野翔太郎, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2022


• Analysis of phage-related genes of Streptomyces under coculture conditions

  永久保利紀, 永久保利紀, 山本達也, 浅水俊平, 浅水俊平, 豊福雅典, 豊福雅典, 野村暢彦, 野村暢彦, 尾仲宏康, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2022


• Study of thiopeptides heterologous production platform focused on transcriptional terminators

  伊地知新太, 永井栄美子, 星野翔太郎, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2022


• Biological significance of the phage tail-like nanostructures produced by soil bacteria

  永久保利紀, 永久保利紀, 浅水俊平, 浅水俊平, 山本達也, 豊福雅典, 豊福雅典, 豊福雅典, 野村暢彦, 野村暢彦, 尾仲宏康, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2022


• Analysis on mechanism of action of goadsporin, a peptide antibiotic targeting growth, secondary metabolism, and sporulation in actinomycetes

  河野佐知子, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2022


• Discovery of actinobacteria drug efflux mechanism mediated by second messenger c-di-GMP

  LEI Yukun, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2022


• Investigation of novel Streptomyces branching inducer

  加藤愛美, 浅水俊平, 浅水俊平, 尾仲宏康, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2022


• Isolation and identification of novel Lipolanthine

  JO Hansaem, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2022


• 放線菌の二次代謝を中心に見た土壌微生物の関わり合い

  浅水俊平

  日本農芸化学会中部支部例会講演要旨集(Web), Nov. 2021


• Analysis of Streptomyces coelicolor TetR family transcriptional regulator involved in RED production delay phenotype during combined-culture

  LEI Yukun, 浅水俊平, 石塚匠, 柳澤昌臣, 大野豊, 佐藤勝也, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2021


• Goadsporin effects on the growth, secondary metabolism, and protein expressions in Streptomyces lividans

  河野佐知子, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2021


• pyrogallol induced bump structure in Streptomyces cells

  加藤愛美, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2021


• Analysis of fatty acyl chain biosynthesis in goadvionins

  小境陵介, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2021


• 薬剤排出様ABCトランスポーターの高発現による複合培養における二次代謝生産応答の遅延機構の解析

  LEI Yukun, 浅水俊平, 石塚匠, 柳澤昌臣, 大野豊, 佐藤勝也, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2021


• 放線菌に広く保存されたファージ尾部様粒子のイメージング解析

  永久保利紀, 浅水俊平, 豊福雅典, 野村暢彦, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2021


• 枯草菌とミコール酸含有細菌によって共生産されるフェノール性化合物が放線菌の分枝を促進する

  加藤愛美, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2021


• 放線菌が生産する新規リポランチン類の探索

  浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2021


• 新規リボソーム翻訳型ペプチド/ポリケタイドハイブリッド化合物・ゴードビオニンの発見とその生合成

  小野拓人, 星野翔太郎, 小境陵介, 高橋秀典, 寺本華奈江, 田中耕一, 阿部郁朗, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2021


• 放線菌が生産する擬似糖鎖の網羅的生合成解析

  角田毅, 伊藤卓也, 浅水俊平, SAMUEL Tanoeyadi, TAIFO Mahmud

  日本放線菌学会大会講演要旨集, Sep. 2021


• 放線菌に対して生育阻害や二次代謝・胞子形成誘導を起こすペプチド系抗生物質goadsporinの作用機構解析

  河野佐知子, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2021


• RNA-seq based analysis of mechanism responsible for activation of secondaty metabolism in combined-culture

  木田優士, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2021


• Streptomyces sp.HEK616とTsukamurella pulmonisとの複合培養での二次代謝活性化機構の解析

  浅水俊平, 尾崎太郎, 西村慎一, 掛谷秀昭, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2019


• 自然共分離放線菌とミコール酸含有細菌の生態学的相互作用の解析

  加藤愛美, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2019


• GNAT superfamily,GdvGの広い基質認識を利用した新規リポペプチド創製

  小境陵介, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2019


• SRP(シグナル認識粒子)を分子標的とした新規抗生物質探索系の確立

  永井栄美子, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2019


• 放線菌の形態異常を引き起こす三種複合培養の解析

  加藤愛美, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2019


• 複合培養におけるStreptomyces sp.HEK616による5aTHQの生産機構

  浅水俊平, 尾崎太郎, 西村慎一, 掛谷秀昭, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2019


• 複合培養における赤色色素生産非応答性変異株の解析

  石塚匠, 浅水俊平, 柳澤昌臣, 佐藤勝也, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2019


• 複合培養により活性化される二次代謝遺伝子プロモーターの制御機構の解析

  桐原正隆, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2019


• N-アセチルトランスフェラーゼ様酵素がポリケチドとランチペプチドの新規結合反応を触媒する

  小境陵介, 菅井佳宣, 寺本和矢, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2019


• ミコール酸含有細菌に対する二次代謝非応答性放線菌変異株の変異点の同定

  浅水俊平, 石塚匠, 柳澤昌臣, 寺本和矢, 佐藤勝也, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2018


• godAプロモーターの複合培養に応答した転写活性化機構の解析

  桐原正隆, 浅水俊平, 寺本和矢, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2018


• 自然共分離株Streptomyces variegatusとMycobacterium septicumの接触相互作用の解析

  加藤愛美, 浅水俊平, 寺本和矢, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2018


• Discovery of a new antibiotic-siderophore hybrid compound from combined-culture of Streptomyces sp. HOK021 and Tsukamurella pulmonis.

  PRAMANA Abrory Agus Cahya, KAWAI Sungjin, KATO Manami, ASAMIZU Shumpei, SUGAI Yoshinori, SUZUKI Hiroaki, ARAKAWA Yoshichika, ONAKA Hiroyasu

  日本農芸化学会大会講演要旨集(Web), Mar. 2018


• 異属細菌間の相互作用がもたらす放線菌特殊代謝

  浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2018


• 舳倉島自然土壌から共分離された放線菌とミコール酸含有細菌の相互作用

  加藤愛美, 浅水俊平, 菅井佳宣, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2018


• 二次代謝誘導ペプチドgoadsporinの作用機構

  金田彬, 尾崎太郎, 菅井佳宣, 浅水俊平, 千田俊哉, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2018


• 新規labionen構造の形成に関与するlanthipeptide合成酵素の解析

  菅井佳宣, 江畑一真, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2018


• 複合培養法を利用した希少放線菌からの生物活性物質探索

  星野翔太郎, 淡川孝義, 浅水俊平, 尾仲宏康, 阿部郁朗

  日本薬学会年会要旨集(CD-ROM), 2018


• Membrane Affinity and Biological Activities of 5aTHQs, Combined-culture Metabolites

  西村慎一, 西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭

  天然有機化合物討論会講演要旨集(Web), 2018


• 自然土壌から共分離された放線菌とミコール酸含有細菌の相互作用の解析

  加藤愛美, 浅水俊平, 菅井佳宣, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2017


• 複合培養によって生産されるテトラヒドロキノリン化合物の解析

  下村杜人, 尾崎太郎, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2017


• Goadsporinとそのターゲットタンパク質Ffhの相互作用の解析

  金田彬, 菅井佳宣, 浅水俊平, 千田俊哉, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2017


• RiPP-polyketideハイブリッド化合物の生合成に関与するGNAT型アシル基転移酵素の解析

  菅井佳宣, 千田美紀, 小野拓人, 浅水俊平, 千田俊哉, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2017


• ミコール酸含有細菌に対する放線菌の網羅的転写応答解析

  浅水俊平, 菅井佳宣, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2017


• 複合培養における放線菌の二次代謝活性化に関与する遺伝子のイオンビームを用いた逆遺伝学的解析

  柳澤昌臣, 浅水俊平, 菅井佳宣, 佐藤勝也, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2017


• 新規RiPPs-ポリケタイドハイブリッド化合物の生合成経路解析

  菅井佳宣, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2017


• 薬剤ターゲットをFfhとするゴードスポリンの新規作用機構解析

  金田彬, 尾崎太郎, 菅井佳宣, 浅水俊平, 千田俊哉, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2017


• 試験管内完全合成系によるゴードスポリン生合成経路の解析とデザイナーアナログ創製

  尾仲宏康, 尾崎太郎, 山下湖奈, 後藤佑樹, 下村杜人, 林昌平, 浅水俊平, 菅井佳宣, 菅裕明

  日本農芸化学会大会講演要旨集(Web), Mar. 2017


• 放線菌の眠れる二次代謝を呼び覚ます!-異属細菌間での競合と協調-

  浅水俊平

  日本生物工学会大会講演要旨集, 2017


• 複合培養法を用いた希少放線菌からの医薬品資源探索

  星野翔太郎, 淡川孝義, 岡田正弘, 浅水俊平, 尾仲宏康, 阿部郁朗

  食品薬学シンポジウム講演要旨集, 2017


• 重イオンビーム遺伝子変異導入法を用いた複合培養による放線菌の二次代謝活性化に関与する遺伝子の探索

  柳澤昌臣, 浅水俊平, 菅井佳宣, 佐藤勝也, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2016


• 複合培養におけるStreptomyces coelicolor A3(2)の経時的トランスクリプトーム解析

  浅水俊平, 佐々木槇子, 尾崎太郎, 菅井佳宣, 宮本憲二, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2016


• 放線菌由来の窒素含有天然物生合成に関する研究

  浅水俊平

  日本放線菌学会大会講演要旨集, Sep. 2016


• 新規ポリケタイド-RiPPsハイブリッド化合物の生合成研究

  菅井佳宣, 小野拓人, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2016


• 無細胞翻訳後系を利用したゴードスポリン生合成経路の再構成と新奇アナログの創製

  尾崎太郎, 山下湖奈, 下村杜人, 後藤佑樹, 菅井佳宣, 浅水俊平, 菅裕明, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2016


• 無細胞翻訳系を用いたラクタゾールの試験管内再構成系の確立

  下村杜人, 尾崎太郎, 菅井佳宣, 浅水俊平, 山下湖奈, 後藤佑樹, 菅裕明, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2016


• 複合培養特異的に生産されるテトラヒドロキノリン生合成遺伝子の解析

  下村杜人, 尾崎太郎, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2016


• RNA-seqによるミコール酸含有細菌に対するStreptomyces coelicolor A3(2)の応答解析

  佐々木槇子, 浅水俊平, 尾崎太郎, 宮本憲二, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2016


• 二次代謝誘導物質ゴードスポリン作用機構の解析

  尾崎太郎, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2016


• ゴードスポリンの酵素的全合成

  山下湖奈, 尾崎太郎, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2016


• 脂質結合性天然物の活用-放線菌複合培養液より見出した新規アルカロイド群に関する研究

  杉山龍介, 西村慎一, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭

  日本薬学会年会要旨集(CD-ROM), 2016


• 微生物の複合培養で得られる5aTHQとstreptoaminalの構造と機能

  西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭

  天然薬物の開発と応用シンポジウム講演要旨集, 2016


• 放線菌由来窒素含有天然生物活性物質の生合成に関する研究

  浅水俊平

  日本農芸化学会関東支部講演要旨集, 2016


• 複合培養における放線菌とミコール酸含有菌の生死で異なる相互作用

  浅水俊平, 尾崎太郎, 寺本華奈江, 佐藤勝也, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2015


• 二次代謝誘導物質ゴードスポリン作用機構の解析

  尾崎太郎, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2015


• Streptomyces sp.TP-A0584由来ゴードスポリン生合成の試験管内再構成系の確立

  山下湖奈, 尾崎太郎, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2015


• 二次代謝誘導物質ゴードスポリンの作用機構の解析

  尾崎太郎, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2015


• goadsporin生合成機構を利用したgoadsporin倍加ペプチドの生産

  岡本悠志, 尾崎太郎, 浅水俊平, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2015


• 複合培養における放線菌二次代謝の誘導要因の探索

  浅水俊平, 尾崎太郎, 佐藤勝也, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2015


• Streptomyces sp.TP-A0584株由来ゴードスポリン生合成のin vitro再構成

  山下湖奈, 尾崎太郎, 浅水俊平, 後藤佑樹, 菅裕明, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2015


• Streptomyces sp.TP-A0584由来ランチペプチド系化合物のゲノムマイニングによる同定

  小野拓人, 江畑一真, 浅水俊平, 尾崎太郎, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2015


• 複合培養を利用した新規テトラヒドロキノリン類の単離とその生合成に関する研究

  尾崎太郎, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2014


• 死細胞は放線菌の二次代謝を複合培養において誘導しない

  浅水俊平, 尾崎太郎, 尾仲宏康

  日本放線菌学会大会講演要旨集, Sep. 2014


• 複合培養において死細胞は放線菌の二次代謝を誘導しない

  浅水俊平, 尾崎太郎, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2014


• 放線菌の複合培養法による新規テトラヒドロキノリン類の単離とその生合成

  尾崎太郎, 森夕希子, 杉山龍介, 西村慎一, 浅水俊平, 掛谷秀昭, 尾仲宏康

  日本農芸化学会大会講演要旨集(Web), Mar. 2014


• ゲノム探索が明らかにした新規32員環チオペプチド,ラクタゾールの構造と生合成

  林昌平, 尾崎太郎, 浅水俊平, 尾仲宏康

  天然有機化合物討論会講演要旨集(Web), 2014


• 異属細菌による放線菌二次代謝産物の誘導

  浅水俊平, 尾仲宏康

  日本農芸化学会関東支部講演要旨集, 2014


• 二次代謝誘導物質ゴードスポリン耐性化機構の解析

  尾崎太郎, 浅水俊平, 尾仲宏康

  日本放線菌学会大会講演要旨集, 2013


• 複合培養に応答するgodAプロモーター領域の解析

  浅水俊平, 小野拓人, 林昌平, 尾崎太郎, 尾仲宏康

  日本放線菌学会大会講演要旨集, 2013

• 日本放線菌学会

  Apr. 2013 - Present


• 日本農芸化学会

  Apr. 2013 - Present

• 放線菌の分枝発生メカニズムの解析と応用

  公益財団法人発酵研究所（IFO）, Apr. 2024 - Mar. 2026


• Biosynthesis of non-natural RiPP-type lipopeptides using enzymatic promiscuity and bioengineering

  2024年度 ノボザイムズ ジャパン研究ファンド, Jan. 2024 - Dec. 2024


• Biosynthesis and mechanistic analysis of Trojan-horse antibiotic from Streptomyces species

  Asamizu Shumpei

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), The University of Tokyo, 01 Apr. 2018 - 31 Mar. 2021

  Sideromycin antibiotics are conjugant of siderophore and antibiotic. Sideromycin-like antibiotic HDM was isolated form the combined-culture of Streptomyces sp. HOK021 and Tsukamurella pulmonis TP-B0596. HDM was a chimeric compound of two units; bacterial FabF inhibitor platensimycin and bacterial siderophore enterobactin, connected through thioester bond. In this study, biosynthetic gene clusters for platensimycin and enterobactin was identified from the complete genome sequence of Streptomyces sp. HOK021. Additionally, physicochemical property of sideromycins including HDMs, salmycins, and ferrimycins in LC-MS/MS were elucidated. Obtained knowledge will be applied for further screening to discover novel sideromycin antibiotics.


• ミコール酸含有細菌の接触刺激による放線菌二次代謝応答機構の変異ゲノム解析を用いた解明

  公益財団法人発酵研究所（IFO）, Apr. 2018 - Mar. 2020, Principal investigator


• 放線菌由来シデロマイシン系抗生物質の生合成及び作用機作解析

  公益財団法人野田産業科学研究所, Apr. 2018 - Mar. 2019, Principal investigator


• Investigation of the molecular mechanism of mycolic acid-containing bacteria involved secondary metabolism activation by Streptomyces species

  Asamizu Shumpei

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), The University of Tokyo, 01 Apr. 2016 - 31 Mar. 2018

  Actinomycetes are producer of valuable secondary metabolites (SM) and are suggested to possess 20-40 of cryptic SM gene clusters. A group of mycolic acid-containing bacteria (MACB) was shown to activate the cryptic gene clusters of actinomycetes, and this project was to identify the gene(s) responsible for the response by Streptomyces to MACB and to elucidate the SM activation mechanism in Streptomyces. Using transcriptomic analysis, we found that the expression variation reached to more than 20% of whole genes in the co-culture by S. coelicolor at 8 hours. We also used heavy ion beam induced mutagenesis of S. coelicolor and screened the response deficient mutants. Among them, we had re-sequenced the mutant genomes of 16 strains and identified several genes responsible for the production of secondary metabolites. We are now targeting the genes responsible for the activation of SM and investigate molecular basis of the response system to MACB by Streptomyces species.


• Analyses of secondary metabolism gene promoters activated by combined-culture

  ASAMIZU Shumpei

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), The University of Tokyo, Apr. 2014 - Mar. 2016

  Secondary metabolites (SMs) produced by actinomycetes are great resources for therapeutic application. Actinomycetes are suggested to possess more than 20 of cryptic gene clusters for SMs production. Our study focus on co-culture method between actinomycetes and mycolic acid-containing bacteria (MACB), that had been shown to activate the cryptic gene clusters of actinomycetes. We used biosynthetic gene cluster of a ribosomal synthesized peptide antibiotic as a model to elucidate the mechanism of activation by stimulation of MACB. Within this specific research project, godA promoter (PgodA) was identified using genetic analyses and colorimetric reporter assay. The sequence of PgodA showed consensus of HrdB. Transcriptomic analyses of co-culture between Streptomyces coelicolor and MACB showed global variations of gene expression by S. coelicolor, suggesting a possibility that overproduction of SMs are as the result of flux balance variations of whole cell metabolism.


• ミコール酸含有細菌による放線菌二次代謝活性化機構に関する研究

  公益信託荒木記念医学・生化学研究振興基金, Apr. 2014 - Mar. 2015, Principal investigator


• インドロカルバゾール生合成機構の解明及び新規類縁体のコンビナトリアル生合成

  浅水 俊平

  日本学術振興会, 科学研究費助成事業 特別研究員奨励費, 特別研究員奨励費, 富山県立大学, 2008 - 2009

  本研究は、微生物が生産する抗癌活性を有するビスインドール化合物に注目し、一つ目に、ビスインドール化合物生合成酵素のX線結晶構造に基づいたアミノ酸置換による新たな酵素機能の開発を目的とし、二つ目に、改変酵素を用いたビスインドール新規類縁体のコンビナトリアル生合成による環境負荷に配慮した生産法の確立を目的としている。これまでに、ビスインドール化合物の詳細な生合成機構を解明するために、スタウロスポリン生合成酵素StaPとビオラセイン生合成酵素VioEのX線結晶構造を明らかにし、StaPとVioEが担う詳細な反応機構を明らかにしている。一方で、明らかになったStaPとVioE反応機構から、アミノ酸置換により、それぞれの酵素反応を改変することは困難であることも示唆された。そこで本年度は、RebCのX線結晶構造に基づき、新たにスタウロスポリン生合成酵素StaCのアミノ酸置換を行い、in vitroでStaC酵素反応を改変することに成功した。StaCはStaPと協調してクロモピロリン酸からK252cを合成するモノオキシゲナーゼホモログである。本酵素の反応機構は未解明な部分が多いが、RebCのX線結晶構造中で基質ポケットを構成する二か所のアミノ酸残基をStaCに導入したところ、RebC型の活性と共に、抗癌剤として臨床開発試験中であるUCN-01の基本骨格である7-hydroxy-K252cを酵素的に生成することを見出した。UCN-01の有効な培養生産法はこれまでになかったことから、本改変StaC酵素を用いることで培養生産が改善出来る可能性が見出された。また、更にインドロカルバゾール化合物の骨格構造の多様性に貢献できると考えられる。

  Competitive research funding