中文摘要：

异戊烯基化吲哚类生物碱广泛存在于麦角菌、青霉菌和曲霉菌中,具有一定的药理学活性,与未异戊烯基化的前体在生物活性方面具有明显的差异.曲霉菌中的某些异戊烯基化吲哚类生物碱具有抗癌活性,如烟曲霉毒素C（fumitremorgin C）、tryprostatin B,但其天然产量低且不易分离,利用化学酶合成法可很容易地将前体转化为异戊烯基化吲哚类生物碱.异戊烯基转移酶FtmPT1对二甲丙烯基二磷酸（dimethylallyl diphosphate,DMAPP）具有专一性,但可以接受不同的芳香族底物.早期研究发现,FtmPT1能接受含色氨酸的不同环二肽为底物,但以cyclo-L-Trp-L-Tyr和cyclo-L-Trp-L-Phe为底物时,酶的相对活性很低,其产物量少,无法用于合成产物.本实验通过优化酶反应条件来提高其产量.将已构建的含ftmPT1的质粒在大肠杆菌中诱导表达,经Ni-NTA亲和柱纯化后用于酶反应.实验结果表明,通过增加酶量（终浓度2.8μmol/L）、延长培养时间（37℃,24h）,以cyclo-L-Trp-L-Tyr和cyclo-L-Trp-L-Phe为底物的酶反应产率分别达到49.3%和21.3%,产物经1H-NMR、^1H-^1H-COSY和ESI-MS鉴定,其结果与预期吻合.据检索,这2个化合物均为新化合物,分别命名为cyclo-C2-1′-DMA-L-Trp-L-Tyr和cyclo-C2-1′-DMA-L-Trp-L-Phe.

英文摘要：

Different from the non-prenylated precursors, prenylated indole alkaloids produced by Claviceps, Penicillium and Aspergillus strains exert diverse biological and pharmacological activities, for examples, fumitremorgin C and tryprostatin B inhibit the growth of a number of tumor cell lines. However, these compounds are usually produced at low concentrations in the natural hosts, thus limits their use in research and development. Chemoenzymatic synthesis has recently been applied to solve this problem. FtmPT1, a prenyhransferase from Aspergillus fumigatus, has a high specificity to dimethylallyl diphosphate （DMAPP）, and is also flexible to tryptophan-containing cyclic dipeptides as the substrates. However, the yields of FtmPT1 react with cyclo-L-Trp-L-Tyr or cyclo-L-Trp-L-Phe was not sufficient for successful production of prenylated compounds in previous studies. In this paper,by increasing the enzyme dose to 2.8 μmol/L and extending the incubation time to 24 hours, the conversion rates of cyclo-L-Trp-L-Tyr or cyclo-L-Trp-L-Phe to their prenylated derivatives was increased to 49.3 % and 21.3 %, respectively, ^1 H-NMR, ^1H-1 H-COSY and ESI-MS analyses confirmed that the products of the enzymatic reactions were cyclo-C2-1′-DMA-L-Trp-L-Tyr and cyelo- C2-1′-DMA-L-Trp-L-Phe, as expected.