产紫青霉G59的超声诱变活性突变株新产抗肿瘤活性产物

目的阐明无活性真菌野生株产紫青霉G59的超声诱变活性突变株N3001d1-1新产抗肿瘤活性产物。方法采用活性跟踪与高效硅胶薄层检测分析相结合的实验方法,组合利用各种色谱技术,通过将突变株样品与原始菌直接比对分离纯化突变株新产活性产物。根据理化性质和波谱数据鉴定化合物结构。用MTT法测试抗肿瘤活性。结果从突变株N3001d1-1发酵物中分离鉴定了2个突变株新产抗肿瘤活性产物,即橘霉素（citrinin）（1）和fructigenine A（2）。化合物1和2对K562细胞均呈抗肿瘤活性,抑制K562细胞的IC50分别为50.6μg/ml和69.1μg/ml。结论化合物1和2均为原始真菌产紫青霉G59所不生产的突变株N3001d1-1新产抗肿瘤活性次级代谢产物。研究结果表明,超声诱变技术可用于改造真菌无活性野生株的次级代谢功能并从中筛选获取活性突变株,从而拓展真菌药源活性新菌株资源。

Antitumor metabolites produced by a bioactive mutant from ultrasound mutagenesis of Penicillium purpurogenum G59

Objective To investigate the antitumor metabolites produced by a bioactive mutant N3001d1-1 from ultrasound mutagenesis of Penicillium purpurogenum G59,a marine-derived wild-type fungal strain without metabolic capability to produce antitumor metabolites.Methods The bioactive metabolites produced by the mutant N3001d1-1 were isolated by a bioassay-guided separation procedure that involved various chromatographic means and direct comparison with the sample from the initial P.purpurogenum G59 strain.The compounds were identified by spectroscopic methods.The antitumor activity was assayed by the MTT method using K562 cells.Results Two antitumor metabolites were isolated and identified as citrinin（1） and fructigenine A（2）,respectively,from the fermentation products of N3001d1-1.Compounds 1 and 2 inhibited the proliferation of K562 cells with the IC50 values of 50.6 and 69.1 μg/ml,respectively.Conclusion Compounds 1 and 2 are antitumor metabolites newly produced by the mutant N3001d1-1,which have not been found in the metabolites of P.purpurogenum so far.The ultrasound-induced mutation technique can alter the secondary metabolism of wild-type fungal strains without bioactivity to obtain bioactive mutants and thus will become a useful method for the expansion of bioactive fungal strain sources for drug screening.