Convenient synthetic approach for tri- and tetraprenylated cyclodipeptides by consecutive enzymatic prenylations
Convenient synthetic approach for tri- and tetraprenylated cyclodipeptides by consecutive enzymatic prenylations
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DOI：
10.1007/s00253-018-8761-7
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发表时间：
2018-03-01
影响因子：
5
通讯作者：
Li, Shu-Ming
中科院分区：
文献类型：
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作者：
Wohlgemuth, Viola;Kindinger, Florian;Li, Shu-Ming
来自橡胶曲霉的烯丙基转移酶EchPT1和EchPT2负责环-l- trp -l- ala的连续烯丙基化，导致形成三烯丙基化的紫锥菊素作为主要产物。在这项研究中，我们证明了EchPT1也接受环- trp - ala和环- trp - pro的所有立体异构体，并在吲哚核上催化区域特异性的反向c2 -戊烯化。EchPT1的产物被EchPT2很好地接受了多次连续的戊酰化，8种底物中的6种的转化率为84 - 98%。C2-、C5-和c7 -三烯基化衍生物是主要的酶产物，其中7种酶产物的产率为40 ~ 86%。四甲基化衍生物在四种反应混合物中具有一个d-和一个l-构型氨基酸残基，其产率高达25-36%，即约占总酶产物的30%。据我们所知，在本研究之前，酶促制备具有如此高效的四烯基化环二肽尚未报道。
The prenyltransferases EchPT1 and EchPT2 from Aspergillus ruber are responsible for the consecutive prenylations of cyclo-l-Trp-l-Ala, leading to the formation of the triprenylated echinulin as the predominant product. In this study, we demonstrate that EchPT1 also accepts all stereoisomers of cyclo-Trp-Ala and cyclo-Trp-Pro and catalyses regiospecific reverse C2-prenylation at the indole nucleus. EchPT1 products were well accepted by EchPT2 for multiple consecutive prenylations, with conversion yields of 84 to 98% for six of the eight substrates. C2-, C5- and C7-triprenylated derivatives are identified as major enzyme products, with product yields of 40 to 86% in seven cases. High product yields of 25-36%, i.e. approximate 30% of the total enzyme products, were observed for tetraprenylated derivatives in the four reaction mixtures with one d- and one l-configured amino acid residues. To the best of our knowledge, enzymatic preparation of tetraprenylated cyclodipeptides with such high efficacy has not been reported prior to this study.