|Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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.