代谢途径抑制剂及前体对海洋红树林内生真菌No.1403产抗肿瘤化合物1403C的影响

Effects of Pathway Enzyme Inhibitors and Precursors on the Anticancer Compound 1403C Synthesis in Halorosellinia sp.(No.1403)

采用酶抑制剂法和前体喂养试验法初步研究了结构新颖的活性蒽醌化合物1403C的合成途径。研究表明,甲羟戊酸合成途径的关键酶抑制剂邻氨基苯甲酸、柠檬酸三钠对单位菌体1403C产量影响比较小;莽草酸途径关键酶氨基苯甲酸合成酶的抑制剂三甲胺在低浓度时(3、6mmol/L)对单位菌体1403C产量没有影响,而高浓度(12mmol/L)时由于较大程度改变发酵液pH而降低了单位菌体1403C产量;莽草酸途径中间产物莽草酸的添加对单位菌体1403C产量没有明显的影响;添加聚酮合成途径聚酮合酶的专一性抑制剂碘乙酰胺对1403C的合成产生强烈的抑制,抑制程度达94.2%;添加丙二酸对1403C的合成有较大的促进作用,单位菌体1403C产量最大增加了59.2%。乙酸钠和丙二酸混合比例为1∶4时对单位菌体1403C产量具有最大促进作用,最大提高量为102.7%。由此推断Halorosellinia sp.(No.1403)可能通过聚酮途径合成1403C。

The biosynthetic pathway for 1403C was studied by feeding pathway specific inhibitors and biosynthetic precursors during the fermentation of Halorosellinia sp.（No.1403）.Results showed that feeding of anthranilic acid and trisodium citrate,specific inhibitors of mevalonate pathway,did not inhibite 1403C yield on biomass（YP/X（1403C））.Addition of low concentration of trimethylamine,inhibitor of shikemate pathway,had no effect on YP/X（1403C）while high concentration（12 mmol/L）of trimethylamine led low YP/X（1403C）compared to the control experiment,because of the low pH in fermentation broth.Feeding of shikimate,key intermediate of shikimate pathway,did not enhance YP/X（1403C）.Addition of iodoacetamide which was the specific inhibitor of the polyketide synthase strongly inhibited the 1403C production with the high inhibition rate of 94.2%.Feeding of malonic acid increased YP/X（1403C）by 59.2% compared to the control.Combined feeding of sodium acetate and malonic acid with a ratio of 1∶4 increased YP/X（1403C）by 102.7%.These results suggested that the biosynthetic pathway of 1403C involved with polyketide pathway.