A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis
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DOI：
10.1073/pnas.0711625105
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发表时间：
2008-02-05
影响因子：
11.1
通讯作者：
Shen, Ben
中科院分区：
文献类型：
--
作者：
Zhang, Jian;Van Lanen, Steven G.;Shen, Ben
烯二炔以其独特的分子结构和作用方式统一起来，代表了迄今为止发现的一些最有效的抗癌药物。据预测，烯二炔核心的生物合成是由与所有已知的 PKS 不同的聚酮合酶 (PKS) 启动的。参与 C-1027 (SgcE) 和新制癌菌素 (NcsE) 生物合成的烯二炔 PKS 的表征现已揭示 (i) PKS 包含中央酰基载体蛋白结构域和 C 端磷酸泛酰乙胺基转移酶结构域； (如果)PKS在异源宿主中具有功能，并且与烯二炔硫酯酶基因共表达，在烯二炔核心生物合成中产生第一个可分离的化合物，1,3,5,7,9,11,13-十五碳庚烯；并且（拟合）SgcE 和 NcsE 的发现可能在所有九元烯二炔中共享，从而支持启动烯二炔生物合成的共同机制。
The enediynes, unified by their unique molecular architecture and mode of action, represent some of the most potent anticancer drugs ever discovered. The biosynthesis of the enediyne core has been predicted to be initiated by a polyketide synthase (PKS) that is distinct from all known PKSs. Characterization of the enediyne PKS involved in C-1027 (SgcE) and neocarzinostatin (NcsE) biosynthesis has now revealed that (i) the PKSs contain a central acyl carrier protein domain and C-terminal phosphopantetheinyl transferase domain; (if) the PKSs are functional in heterologous hosts, and coexpression with an enediyne thioesterase gene produces the first isolable compound, 1,3,5,7,9,11,13-pentadecaheptaene, in enediyne core biosynthesis; and (fit) the findings for SgcE and NcsE are likely shared among all nine-membered enediynes, thereby supporting a common mechanism to initiate enediyne biosynthesis.