Entomopathogenic fungi seem to be interesting as a source of biologically active compounds such as an insecticides1) and immunosuppressants2,3), because all insect orders are susceptible to fungal diseases. With the goal of finding novel bioactive compounds from fungi, we investigated metabolite diversity using an HPLC screening program. During the screening process, we isolated two novel metabolites named pyridovericin (1) and pyridomacrolidin (2) (Fig.

Sir: Many entomopathogenic fungi are presumed to cause host death through the inhibition of enzymes and interference with the regulatory system in the host by production of toxic fungal metabolites and pathogenic classified into five genera: Oomycota, Chytridiomycota, Zygomycota, Ascomycota, and Deuteromycota, and Deuteromycota seems to be preferred as a source of screening for new bioactive compounds from fungal metabolites as fungi can be cultured on artificial media. of Health, for assay for protein tyrosine kinase.

A new melanin biosynthesis inhibitor, melanoxazal, was isolated from the fermentation broth of Trichoderma sp. ATF-45 1 by successive purification procedures of carbon adsorption, ethyl acetate extraction and silica gel column chromatography. The inhibitor possesses a novel oxazole-containing structure with molecular formula, C8H9NO3. The structure was determined by means of NMR analyses to be (£)-4-(2'-formyl-3'-hydroxybuten-r-yl) oxazole, which is related to melanoxadin. Melanoxazal inhibited melanin formation in the larval haemolymph of the silkworm, Bombyx mori; [C50 value= 30.1 /ig/ml. Melanoxazal also showed a strong inhibitory activity against mushroom tyrosinase with IC50 value=4.2 wg/ml.Tyrosinase mediated melanin biosynthesis in insects has been considered to involve three key reactions: the monophenoloxidase (tyrosinase) catalyzed oxidation of tyrosine to 3,4-dihydroxyphenylalanine (dopa) in the first step, the diphenoloxidase catalyzed conversion of dopa to dopachrome via dopaquinone in second step, and formation of melanin by spontaneous polymerization of dopachrome in third step.1} Several investigations on melanin biosynthesis inhibitors of microbial origin, feldamycin,2) melanostatin,3'4) albocycline, OH-3984 Kl and K2,5'6) MR304A7) have been reported with screening methods using mushroomtyrosinase, melanin formation in Streptomyces bikiniensis and B16 melanoma cells. We have previously reported our screening program for melanin biosynthesis inhibitors from microorganisms, using the larval haemolymph of the silkworm, Bombyx rnori, in which we have isolated melanoxadin8) (2) and trichoviridin9) (3) from the cultured broth of fungal strains ATF-606and ATF-287,respectively. This method is advantageous in that it can screen manysamples in a shorter time than other methods. Furthermore, this screening method provides a useful approach in that it can find novel enzymatic inhibitors, because it contains a wider variety of enzymatic systems in the melanin metabolic pathway than the other single enzymatic systems. During the course of searching for melanin biosynthesis inhibitors, a novel oxazole compounddesignated as melanoxazal (1) (Fig. 1) was isolated from fungi. Taxonomical study indicated that the producing organism was Trichoderma sp. ATF-451.Structural studies of 1 showed that it possesses an oxazole skeleton with a molecular formula of C8H9NO3 which is struc- Fig. 1. The structures of melanoxazal (1), melanoxadin (2) and trichoviridin (3).

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