Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine
Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine
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DOI：
10.1021/ja056231t
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发表时间：
2006-03-08
影响因子：
15
通讯作者：
Rajski, SR
中科院分区：
文献类型：
--
作者：
Zhang, CS;Weller, RL;Rajski, SR
带有 5'-氮丙啶或 5'-N-芥末亲电子试剂的腺苷类似物是甲基转移酶依赖性 DNA 烷化剂。我们在这里提出了一种带有 5'-氨基酸 N-芥末侧链的新型合成辅因子。与之前研究的合成辅因子不同，这种材料可以被天然产物生物合成酶瑞贝卡霉素甲基转移酶 (RebM) 非常有效地利用，生成许多新的瑞贝卡霉素类似物。这些数据促进了这样的观念：天然产物甲基转移酶可以与非天然辅因子一起使用，以增强天然产物类似物的分子多样性，用于药物发现。据我们所知，这是除 DNA 甲基转移酶之外第一个可以利用此类合成辅因子的生物甲基转移酶的文献。
Adenosine analogues bearing either 5‘-aziridine or 5‘-N-mustard electrophiles are methyltransferase-dependent DNA alkylating agents. We present here a novel synthetic cofactor bearing a pendant 5‘-amino acidN-mustard. Unlike previously studied synthetic cofactors, this material is very efficiently used by the natural product biosynthetic enzyme rebeccamycin methyltransferase (RebM) to generate a number of new rebeccamycin analogues. These data promote the notion that natural product methyltransferases can be used with non-natural cofactors to enhance the molecular diversity of natural product analogues for drug discovery. To our knowledge, this is the first documentation of a biological methyltransferase, other than DNA methyltransferases, that can exploit such synthetic cofactors.