Biochemical studies on cell growth stimulating substances of low molecular weight produced by microorganisms

微生物产生的低分子量细胞生长刺激物质的生化研究

基本信息

  • 批准号:
    03453141
  • 负责人:
  • 金额:
    $ 0.96万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
  • 财政年份:
    1991
  • 资助国家:
    日本
  • 起止时间:
    1991 至 1993
  • 项目状态:
    已结题

项目摘要

None proteinous microbial metabolites with low molecular weight are expected to be useful for studying cell growth mechanisms as well as for reducing production cost of proteins such as growth factors and hormones produced by animal cells. Our screening for such compounds resulted in isolation of four unique metabolites; lavanducyanin from Streptomyces aeriouvifer, exfoliazone from Streptomyces exfoliatus, resorcinin from a gliding bacterium, Cytophaga johnsonae and misakimycin from Streptomyces misakiensis. All of these metabolites were lipophilic and purified by solvent extraction followed by appropriate chromatographies. Their structures were determined mainly based on NMR spectral analysis to be as follows; lavanducyanin, a phenazine derivative with an alkyl substituent; exfoliazone, a substituted phenoxazinone; resorcinin, 2-isoundecy1-5-isohexyl-resorcinol; misakimycin, 5-hydroxy-2,7-dimethoxy-6-methyl-1,4-naphthoquinone.These derivatives showed strong growth promoting activities to some kind of animal cell lines at lower serum concentrations. However, no effect was observed under serum-free conditions. Their activities were analyzed by MTT assay and by the increases of cell number and DNA synthesis, and their effective doses were determined at the range of nanogram to microgram/ml.Since the growth stimulating effect were observed with same kinds of cell lines including RLN-8, NIH 3T3 and T601, their action mechanisms seem to be identical. Since the famous tumor promoter TPA was inactive under the same condition, the action mechanisms of the compounds isolated by this work are concluded to be different from that of TPA.
具有低分子量的非蛋白质微生物代谢物预期可用于研究细胞生长机制以及用于降低由动物细胞产生的蛋白质如生长因子和激素的生产成本。我们对这些化合物的筛选导致了四种独特的代谢产物的分离;从Streptomyces aeriouvifer中分离出lavanducyanin,从Streptomyces exfoliatus中分离出exfoliazone,从滑行细菌中分离出间苯二酚,从Streptomyces misakiensis中分离出Cytophaga johnsonae和misakimycin。所有这些代谢产物均为亲脂性,并通过溶剂提取和适当的色谱法进行纯化。通过核磁共振谱分析,确定了它们的结构:lavanducyanin,一种含烷基取代的吩嗪衍生物; exfoliazone,一种取代的吩恶嗪酮; resorcinin,2-isundecyl-5-isohexyl-resorcinol; misakimycin,5-hydroxy-2,7-dimethoxy-6-methyl-1,4-naphthoquinone。然而,在无血清条件下没有观察到任何效果。用MTT法、细胞计数法和DNA合成法测定了它们的活性,并确定了它们的有效剂量范围为ng ~ μ g/ml。由于它们对同种细胞系RLN-8、NIH 3 T3和T601均有促生长作用,因此它们的作用机制似乎是一致的。由于著名的肿瘤促进剂TPA在相同条件下无活性,因此本工作所分离的化合物的作用机制与TPA不同。

项目成果

期刊论文数量(26)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
S.Imai: "Exfoliazone and lavanducyanin,potent growth promoting substances of rat liver cell line,RLNー8,produced by Steptomyces exfoliatus and Streptomyces aeriouvifer." J.Antibiotics. 45. (1992)
S.Imai:“Exfoliazone 和 lavanducyanin,大鼠肝细胞系 RLN-8 的有效生长促进物质,由脱叶链霉菌和链霉菌产生。”J.Antibiotics 45。
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    0
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S.Imai: "Studies on cell growth stimulating substances of low molecular weight.Part2.exfoliazone and lavanducyanin,potent growth promoting substances of rat liver cell line,rln-8,produced by Streptomyces exfoliatus and Streptomyces aeriouvifer" J.Antibiot
S.Imai:“低分子量细胞生长刺激物质的研究。第 2 部分。exfoliazone 和 lavanducyanin,大鼠肝细胞系,rln-8 的有效生长促进物质,由脱叶链霉菌和链霉菌产生” J.Antibiot
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    0
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K.Fujioka: "Studies on cell growth stimulating substances of low molecular weight.Part4.Misakimycin,mammalian cell growth stimulating substance produced by Streptomyces misakiensis" J.Antibiotics. 45. (1992)
K.Fujioka:“低分子量细胞生长刺激物质的研究。第四部分。三崎霉素,由三崎链霉菌产生的哺乳动物细胞生长刺激物质”J.抗生素。
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    0
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S.Imai: "Studies on cell growth stimulating substances of low molecular weight.Part 2.exfoliazone and lavanducyanin,potent growth promoting substances of rat liver cell line,rin-8,produced by Streptomyces exfoliatus and Streptomyces aeriouvifer." J.Antibi
S.Imai:“低分子量细胞生长刺激物质的研究。第 2 部分。exfoliazone 和 lavanducyanin,大鼠肝细胞系的有效生长促进物质,rin-8,由脱叶链霉菌和空气链霉菌产生。”
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    0
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S.Imai: "Studies on cell growth stimulating substances of low molecular weight.Part3.Resorcinin,a mammalian cell growth stimulating substance produced by Cytophaga Johnsonae." J.Antibiotics. 46. (1993)
S.Imai:“低分子量细胞生长刺激物质的研究。第三部分。间苯二酚,一种由 Cytophaga Johnsonae 产生的哺乳动物细胞生长刺激物质。”
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SETO Haruo其他文献

SETO Haruo的其他文献

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{{ truncateString('SETO Haruo', 18)}}的其他基金

Studies on terpenoids produced by actinomycetes-Screening for new bioactive compounds
放线菌产生的萜类化合物的研究——新型生物活性化合物的筛选
  • 批准号:
    14360067
  • 财政年份:
    2002
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Biosynthetic studies on terpenoids produced by Actinomycetes by focusing on the nonmevalonate pathway
以非甲羟戊酸途径为重点的放线菌产生的萜类化合物的生物合成研究
  • 批准号:
    10460047
  • 财政年份:
    1998
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Biosynthetic Studies of terpenoids produced by actinomycetes
放线菌产生的萜类化合物的生物合成研究
  • 批准号:
    08456057
  • 财政年份:
    1996
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
DEVELOPMENT OF NEW NMR TECHNIQUES AND THEIR APPLICATION TO STRUCTURAL ANALYSIS OF NATURAL PRODUCTS
新核磁共振技术的开发及其在天然产物结构分析中的应用
  • 批准号:
    06556019
  • 财政年份:
    1994
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)
Biosynthetic Studies of C-P Compounds by the Use of a New Gene Modification Technique
利用新的基因修饰技术进行 C-P 化合物的生物合成研究
  • 批准号:
    01470127
  • 财政年份:
    1989
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Development of highly sensitive NMR spectroscopic techniques and their application to structural analysis of natural products
高灵敏度核磁共振波谱技术的发展及其在天然产物结构分析中的应用
  • 批准号:
    62860014
  • 财政年份:
    1987
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research
Bioorganic Chemical Studies on the Formation Mechanisms of Bioactic C-P Compounds
生物活性C-P化合物形成机制的生物有机化学研究
  • 批准号:
    61470133
  • 财政年份:
    1986
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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放線菌の生産するラバンドリル基を持つフェナジン化合物の生合成研究
放线菌产生的薰衣草基吩嗪类化合物的生物合成研究
  • 批准号:
    06F06430
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  • 批准号:
    06660128
  • 财政年份:
    1994
  • 资助金额:
    $ 0.96万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
天然物由来制癌物質の探索とその化学的誘導に関する研究
寻找天然来源的抗癌物质及其化学诱导研究
  • 批准号:
    01010018
  • 财政年份:
    1989
  • 资助金额:
    $ 0.96万
  • 项目类别:
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