An antibiotic factory caught in action
An antibiotic factory caught in action
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DOI：
10.1038/nsmb808
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发表时间：
2004-09-01
影响因子：
16.8
通讯作者：
Stroud, RM
中科院分区：
文献类型：
--
作者：
Keatinge-Clay, A;Maltby, DA;Stroud, RM
芳香族聚酮化合物如放线菌紫素、四环素和阿霉素的合成始于聚酮化合物链的形成。在II型聚酮酶（PKS）中，链通过异二聚酮合酶-链长因子（KS-CLF）聚合。在这里，我们提出了2.0埃结构的放线菌紫素KS-CLF，这表明聚酮被拉长的两亲性隧道内类似于17埃的长度在异二聚体界面。该结构解决了许多关于KS和CLF作用的问题。虽然CLF调节链长，但它没有活性位点; KS必须催化链起始和延伸。我们提供的证据表明，第一环化的聚酮发生在KS-CLF隧道。这个中心PKS聚合酶的机制细节可以指导生物合成化学家设计新的药物和聚合物。
The synthesis of aromatic polyketides, such as actinorhodin, tetracycline and doxorubicin, begins with the formation of a polyketide chain. In type II polyketide synthases (PKSs), chains are polymerized by the heterodimeric ketosynthase - chain length factor (KS-CLF). Here we present the 2.0-Angstrom structure of the actinorhodin KS-CLF, which shows polyketides being elongated inside an amphipathic tunnel similar to 17 Angstrom in length at the heterodimer interface. The structure resolves many of the questions about the roles of KS and CLF. Although CLF regulates chain length, it does not have an active site; KS must catalyze both chain initiation and elongation. We provide evidence that the first cyclization of the polyketide occurs within the KS-CLF tunnel. The mechanistic details of this central PKS polymerase could guide biosynthetic chemists in designing new pharmaceuticals and polymers.