41 インドールアルカロイド発癌プロモーター・テレオシジンの生合成(口頭発表の部)  [in Japanese] 41 STUDIES ON THE BIOSYNTHESIS OF INDOLE ALKALOID TUMOR PROMOTER TELEOCIDIN  [in Japanese]

Teleocidins produced by actinomycetes are potent tumor promoters and peculiar indole alkaloids containing a nine-membered lactam ring and a complex monoterpenoid moiety. Among the teleocidin-producing actinomycetes, Streptoverticillium blastmyceticum NA34-17, which we had found to produce the Epstein-Barr virus early antigen inducing indole alkaloids, has a characteristic feature of producing (-)-indolactam V (1), the common biosynthetic intermediate of teleocidins, in quantity. This characteristic would be advantageous to obtain a wide variety of biosynthetic intermediates of teleocidins. Using this microorganism, the possible biosynthetic pathway of teleocidins shown in Fig. 8 was proposed by feeding experiments with several D or ^<13>C-labelled precursors and isolation of new teleocidin-related metabolites named blastmycetin D (8) and E (9). Feeding experiments with several D or ^<13>C-labelled amino acids and possible biosynthetic precursor showed that (-)-indolactam V (1) was biosynthesized from L-tryptophan, L-valine and L-methionine via N-methyl-L-valyl-L-tryptophanol (3). From the isolation of blastmycetin D (8) and E (9), and feeding experiments with D-labelled L-methionine, we proposed the hypothesis that (-)-N^1-nerylindolactam V was a common biosynthetic intermediate of teleocidins, and that the complex monoterpenoid moieties of teleocidins, for example those of olivoretin A, C and E (see Fig. 8), arose by difference of the sequence of the methylation and the aza-Claisen rearrangement, and the position of the methylation.