1993 Fiscal Year Final Research Report Summary
Finding of new bioactive compounds from microorganisms, on the base of biosyunthetic studies on microbial secondary metabolites.
| Project/Area Number |
04671309
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
NAKAGAWA Akira Teikyo University, Bioscience, Professor, 理工学部, 教授 (60050548)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Senji Teikyo University, Bioscience, Research Associate, 理工学部, 助手 (00236291)
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| Project Period (FY) |
1992 – 1993
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| Keywords | polyketide / fungi / biosynthesis / chemical screening / melanin biosynthesis inhibitor / C^<13> labeled compound / neuritogenesis |
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| Research Abstract |
We have reported the biosyntheses of new bioactive compounds from microbial secondary metabolites. Taking into consideration the findings on the biosynthetic studies, new screening systems, a chemical screening and melanin biosynthesis inhibitor were introduced to search for a novel compound from fungal metabolites. A new compound, ATF-202, in addition to identification of purified compounds with known metabolites such as radicicol, kotanin and chrodrimanin B was found by chemical screening for novel polyketides with a characteristic UV absorption. In the screening program of a melanin biosynthesis inhibitor using larval haemolymph of silkworm, Bombyx mori, ATF-287 and ATF-606 were isolated as a biologically active compound among 700 strains of fungi. ATF-287 which shows a potent inhibitory activity in silkworm melanin biosynthesis and mushroom tyrosinase was identified with an antibacterial antibiotic, trichoviridin. The inhibitory activity of trichoviridin is first findings. On the other hand, ATF-606 was isolated as a new compound with an oxazole skeleton. In vivo evaluation of this compund is under investigation.
Biosynthetic study of lactacystin, a nobel microbial metabolite which induces differentiation of Neuro 2A cells, a mouse neuroblastoma cell line was carried out using C^<13> labeled compounds and NMR spectroscopic analysis. The feeding experiments of L-[2-C^<13>] leucine, [1-C^<13>] isobutyrate and L, L'-[1,1'-C^13_] cystine indicated that lactacystin is biosynthesized from three units, L-leucine, isobutyrate and L-cysteine. Furthermore, the feeding experiment of C^<13> labeled L-leucine derived from [U-C^13_) glucose provided the evidence that two diastereotopic methyl groups, C-11 and C-12 of lactacystin are assignable to pro R and pro S, respectively.
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