放線菌の分子遺伝学に関する日英共同研究

1998 年度 実績報告書

• 研究課題/領域番号: 09044205
• 研究機関: 東京大学
• 研究代表者: 堀之内 末治 東京大学, 大学院・農学生命科学研究科, 教授 (80143410)
• 研究分担者: 池田 治生 北里大学, 薬学部, 助教授 (90159632) ; 小河原 宏 明治薬科大学, 薬学部, 教授 (00097198) ; 山田 靖宙 大阪大学, 工学部, 教授 (00011891) ; 瀬戸 治男 東京大学, 分子細胞生物学研究所, 教授 (10013335) ; 別府 輝彦 日本大学, 生物資源科学部, 教授 (80011873)
• キーワード: Japan-UK Joint Study / Streptomyces / 分子生物学 / 抗生物質生産 / 遺伝子工学 / 分子育種 / 二次代謝 / 形態分化

研究概要

本研究は放線菌の抗生物質生産、形態分化の調節機構を分子レベルで解明し、その成果を菌株改良の分子育種に結びつけるべく、英国のジョンイネス研究所の研究者との共同研究を行うものである。日本側から15名が参加した昨年度のジョンイネス研究所でのワークショップ(放線菌の分子生物学に関するワークショップ)において、互いの情報交換、共同研究の進め方について討論を行った結果、本年度は日本側で多くの協同研究が行われた。本年度秋には日本側研究者の代表として堀之内がジョンイネス研究所を訪れ、共同研究の成果を発表しあい、さらには将来にわたる共同研究の進め方を話し合った。分坦研究者である大西は4月から5月にかけて約3週間、ジョンイネス研究所にて実験を行い、Hopwood教授、Bibb教授との共同研究を進めた。一方、英国側の共同研究者であるHopwood教授、Chater教授、Bibb教授の3人はそれぞれ個別に来日し、日本側研究者と情報交換を行った。このような活発な共同研究の成果を共同研究報告書としてまとめ、関連機関に送付した。特筆すべき協同研究の成果として、あえて1つを選ぶならば、Bibb教授のグループと大阪大学の山田グループとの間で行われたStreptomyces coelicolorの抗生物質生産を誘導する低分子物質の単離と構造決定およびその受容体の遺伝子クローニングがあげられる。放線菌研究において世界をリードする我が国と英国の研究者間の共同研究体制がより強固なものになったことで本研究課題の目的は十分に達成されたと考える。

研究成果

• [文献書誌] Sugiyama,M.: "Site-directed mutagenesis of the A-factor receptor protein: Val-41 important for DNA-binding and Trp-119 important for ligand-binding" Gene. 222. 133-144 (1998)
• [文献書誌] Ueda,K: "Characterization of an A-factor-responsive repressor for amR essential for onset of acrial myeclium formation in Strep-tomyces grlscus" J.Bacteriol.180. 5085-5093 (1998)
• [文献書誌] Onaka,H.: "Involvement of two A-factor receptor homologucs in Streptomyces coelicolor A3(2) in the regulation of secondary metabolism and morphogenesis" Mol.Microbiol.28. 743-753 (1998)
• [文献書誌] Ando,N.: "Gene organization in a 12-kilobase region covering afsA cncoding an A-factor biosynthetic enzyme" Actinomycetol.12. 40-45 (1998)
• [文献書誌] Hong,S.-K.: "Effects of protein kinase inhibitors on in vitro protein phosphorylation and on secondary mclabolism and morphogenesis in Streptomyces coclicolor A3(2)" J.Microbiol.Biotechnol.8. 325-332 (1998)
• [文献書誌] Kang,D.-K.: "Possible involvement of cAMP in acrial mycelium formation and secondary metabolism in Streptomyces griscus" Microbiology. (in press). (1999)
• [文献書誌] Tin-Wein Yu: "Engincered biosynthesis of novel polyketides from Streptomyces spore pigment polykeide synthases" J.Am.Chem.Soc.120. 7749-7759 (1998)
• [文献書誌] Chong,P.P.: "Plysical identification of a chromosomal locus encoding biosynthetic genes for the lipopeptide calcium-dependent anti-blotie(CDA) of Streptomyces eoelicotor A3(2)" Microbiology. 144. 193-199 (1998)
• [文献書誌] Tropf,S.: "Heterologously expressed acyl carrier protein domain of rat fatty acid synthase functions in Escherichia coli fatty acid synthase and Streptomyces coelicolor polyketide synthase systems" Chemistry & Biology. 5. 135-146 (1998)
• [文献書誌] Ichinose,K.: "The granaticin biosynthetic gene cluster of Streptomyces violaeeoruber Tu22:sequence analysis and expression in a heterologous host" Chemistry & Biology. 5. 647-659 (1998)
• [文献書誌] Ryding,N.J.: "A developmentally regulated gene encoding a repressor-like protein is essential for sporulation in Streptomyces eoelicolor A3(2)" Mol.Microbiol.29. 343-357 (1998)
• [文献書誌] 〓,H.: "The Streotimyces coelicolor sporulation-specific owen form of RNA polymerase transcribes a gene encoding a ProX-like protein that is dispensable for sporulation" Gene. 212. 137-146 (1998)
• [文献書誌] Chater,K.F.: "Taking a genetic scalpel to the Streptomyces colony" Microbiology. 144. 1465-1478 (1998)
• [文献書誌] Elliot,M.: "The bldD gene of Streptomyces coelicolor A3(2):a regulatory gene involved in morphogenesis and antibiotic production" J.Bacteriol.180. 1549-1555 (1998)
• [文献書誌] Kelemen,G.: "Developmental regulation of transcription of whiE,a locus specifying the polyketide spore pigment in Streptomyces coelicolor A3(2)" J.Bacteriol.180. 2515-2521 (1998)
• [文献書誌] Takahashi,S.: "A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catelyzing the formation of 2-C-methyl-D-eryth-ritol 4-phosphate in an ahemative nonmevalonate pathway for terpen" Proc.Natl.Acad.Sci.USA. 95. 9879-9884 (1998)
• [文献書誌] Kuzuyama,T.: "Direct formation of 2-C-methyl-D-crythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate by 1-deoxy-D-xylu-lose 5‐phosphate reductoisomerase,a new cnzyme in the non-mevalonate pathway to isopentenyl diphosphate" Tetrahedron Lett.39. 4509-4512 (1998)
• [文献書誌] Orihara,N.: "Studies on the biosynthesis of terpenoid compounds produced by actinomycetes.3.Biosynthesis of the iso-prenoid side chain of novobiocin via the non-mcvalonate pathway in Streptomyces niveus" J.Antibiot.51. 676-678 (1998)
• [文献書誌] Kuzuyama,T.: "Fosmidomycin,a specific inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in the nonmcvalonate pathway for terpenoid biosynthesis" Tetrahedron Lett.39. 7913-7916 (1998)
• [文献書誌] Seto,H.: "Studies on the biosynthesis of terpenoids produced by actinomycetes.Part-4.Formation of BE-40644 by the mevalonate and nonmevalonate pathways" Tetrahedron Lett.39. 9497-9500 (1998)
• [文献書誌] Takahashi,S.: "Purification,characterization,and cloning of a cubacterial 3-hydroxy-3-methylglutaryl coenzyme A reductase,a key enzyme involved in biosynthesis of terpenoids" J.Bacteriol.(in press). (1999)
• [文献書誌] Kuzuyama,T.: "Construction and characterization of Escherichia coli disruptants defective in the yacM gene" Biosci.Biotechnol.Biochem.(in press). (1999)
• [文献書誌] Hotta.K.: "The novel enzymatic 3"-N-acetylation of arbekacin by an aminoglycoside 3-N-acetyltransferase of Streptomyces origin and the resulting activity" J.Antibiot.51. 735-742 (1998)
• [文献書誌] Ueda,K.: "Two distinct mechanisms cause heterogeneity of 16S rRNA" J.Bacteriol.181. 78-82 (1999)
• [文献書誌] Ikeda,H.: "Cloning of the gene encoding avermectin B 5-O-methyltransferase in avermectin-producing Streptomyces avemitilis" Gene. 206. 175-180 (1998)
• [文献書誌] Guthrie,E.P.: "A response-regulator-like activator of anlibiotic synthesis from Streptomyces eoelicolor A3(2) with an amino-terminal domain that lacks a phosphorylation pocket" Microbiology. 144. 727-738 (1998)
• [文献書誌] Kang,S.G.: "Actinorhodin and undecylprodigiosin production in wild-type and relA mutant strains of Streptomyces coelicolor A3(2) grown in continuous culture" FEMS Microbiol.Lett.168. 221-226 (1998)
• [文献書誌] Redenbach,M.: "Cloning and physical mapping of the EcoRI fragments of the giant linear plasmid SCP1" J.Bacteriol.180. 2796-2799 (1998)
• [文献書誌] Kinashi,H.: "Physical mapping of the linear plasmid pSLA2-L and localization of the cryAf and actl homologs" Biosci.Biotechnol.Biochem.62. 1892-1897 (1998)
• [文献書誌] Hirakata,T.: "Putative protein serine/threonine kinase genes are located in several positions on the chromosome of Streptomyces coelicolor A3(2)." FEMS Microbiol Lett.159. 1-5 (1998)
• [文献書誌] Itohara,T.: "Preliminary proteome analysis of membrane proteins in Streptomyces coelicolor A3(2)" Actinomycetologica. (in press). (1999)
• [文献書誌] Nakano,H.: "Gene replacement analysis of the Streptomyces virgineae barA gene encoding the butyrolactone autoregulator receptor reveals that BarA acts as a repressor in virginiamycin biosynthesis" J.Bacteriol.180. 3317-3322 (1998)
• [文献書誌] Suzuki,N.: "Purification and characterization of virginiamyein Ml reductase from Streptomyces virginiac" Antimicrob.Agents Chemother.42. 2985-2988 (1998)
• [文献書誌] Okamoto,S.: "In vitro protein phosphorylation associated with cellular differemiation of Streptomyces griseus" Arch.Microbiol.169. 174-177 (1998)
• [文献書誌] Ochi,K.: "Genetic mapping and characterization of novel mutations which suppress the effect of a relC mutation on antibiotic production in Streptomyces coelicotor A3(2)" J.Antibiot.51. 592-595 (1998)
• [文献書誌] Kawamoto,S.: "Comparative ribosomal protein(L11 and L30) sequence analyses of several Strptomyces spp.commonly used in genetic studies" Int.J.Sys.Bacteriol.48. 597-600 (1998)
• [文献書誌] Hosoya,Y.: "Acquisition of certain streptomycin-resistant(slr) mutations cnhances antibiotic production in bacteria" Antimicrob.Agents Chemother.42. 2041-2047 (1998)
• [文献書誌] Okamoto,S.: "An essential GTP-binding protein functions as a regulator for differentiation in Streptomyces coelicolor" Mol.Microbiol.30. 107-119 (1998)
• [文献書誌] Kawamoto,S.: "Sequence analysis of the ribosomal L11 protein gene(rplK=relC) in Streptomyces lavendulac using a deletion allele" J.Antibiot.51. 954-957 (1998)
• [文献書誌] Han,W.-D.: "A novel sporulation-control gene(spoOM) of Bacilus subtilis with a On-regulated promoter" Gene. 217. 31-40 (1998)
• [文献書誌] Ichinose,K.: "Biosynthetic gene cluster of benzoisochromanequinone antibiotics in Streptomyces spp:identification of genes involved in post-PKS tailoring steps" Actinomycetol.12. 99-109 (1998)
• [文献書誌] Ichinose,K.: "Proof that the actV1 genetic region of Streptomyces coelicolor A3(2) is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin" Bioorg.Med.Chem.Lett.9. 395-400 (1999)
• [文献書誌] 岡本 晋: "微生物の形態分化に関与するGTP結合タンパク質" 生物工学会誌. 76. 72-75 (1998)
• [文献書誌] 瀬戸 治男: "微生物が行うユニークな化学反応--C-P化合物の生合成機構" 日本農芸化学会誌. 72. 1-18 (1998)
• [文献書誌] 川本 伸一: "放線菌における二次代謝と緊縮制御" 化学と生物. 36. 144-145 (1998)
• [文献書誌] 堀田 国元: "放線菌のアミノグリコシド抗生物質多剤耐性とその応用" 生物工学会誌. 76. 76-81 (1998)
• [文献書誌] 堀田 国元: "アミノ配糖体の耐性機序" 医薬ジャーナル. 34. 65-74 (1999)
• [文献書誌] 〓田 治生: "コンビナトリアル・バイオシンセシス〜ポリケチド化合物を例として" 蛋白質・核酸・酵素. 43. 49-61 (1998)
• [文献書誌] 木梨 陽康: "放線菌の線状染色体のダイナミックな構造変化と染色体の起源・進化" 蛋白質・核酸・酵素. 43. 1453-1460 (1998)
• [文献書誌] Horinouchi,S.: "Cell‐Cell Communication in Bacteria" G.M.Dunny and S.C.Winans(eds.) American Society for Microbiology,Washington.D.C.(in press), (1999)