Antitumor metabolites produced by two Penicillium purpurogenum G59 mutants / 国际药学研究杂志

Objective: To investigate the antitumor metabolites of fungal mutants 2-2-3 and PDN-f-2, the two bioactive mutants of Penicillium purpurogenum G59 that do not produce antitumor metabolites. Methods: Bioactive metabolites newly produced by the mutants were isolated by a bioassay-guided separation procedure using iquid-liquid extraction, column chromatography and recrystallization methods through direct comparison with the sample from P. purpurogenum G59. The compounds obtained were identified by spectroscopic methods. The antitumor activity was assayed by the MTT method using K562 cells. Results: Two bioactive metabolites 1 and 2 were isolated from the fermentation products of 2-2-3 and PDN-f-2, respectively, and identified as ergone (1) and citrinin (2). Compounds 1 and 2 inhibited the proliferation of K562 cells with the IC50 values of 7. 4 and 48. 0 μg/ml, respectively. Conclusion: Compounds 1 and 2 are the antitumor metabolites newly produced by he mutants 2-2-3 and PDN-f-2, respectively, and have not been found in the metabolites of P. purpurogenum so far. It is revealed from the present result that the alteration of secondary metabolism of wild-type fungal strains without bioactivity for obtaining bioactive metabolite-producing mutants may become a new route to expand the source of new fungal strains for drug screening.

Improvement of Ergone Production from Mycelial Culture of Polyporus umbellatus

Ergone,a fungal metabolite derived from ergosterol,was previously isolated and identified from Polyporus umbellatus. Ergone is a major component of P. umbellatus known to have anti-aldosteronic diuretic effect and also displays cytotoxic activities. Most of mushroom's fruit bodies used for test contained less than 10 microg/g of ergone. But P. umbellatus have larger amount of ergone than any other mushrooms. In order to improve the ergone production from the submerged culture of P. umbellatus, several factors including medium composition,culture conditions (temperature and pH) and different combinations of co-cultivation with various mycelia were studied. Among various carbon sources examined,starch proved to be most effective for the production of mycelia. The optimum pH and temperature for a flask culture of P. umbellatus mycelia were found to be 4.5 and 25degrees C,respectively. Under the optimized culture conditions,both the ergone production (86.9 microg/g) and mycelial growth (3.5 g/l) increased when P. umbellatus was cultured with Armillariella mellea. When the optimized conditions were applied,both mycelium and ergone production were significantly enhanced.