Cis-Double Bond Formation by Thioesterase and Transfer by Ketosynthase in FR901464 Biosynthesis
Cis-Double Bond Formation by Thioesterase and Transfer by Ketosynthase in FR901464 Biosynthesis
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FR901464生物合成中硫酯酶形成顺式双键和酮合酶转移
DOI：
10.1021/ja500942y
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发表时间：
2014-03-26
影响因子：
15
通讯作者：
Tang, Gong-Li
中科院分区：
文献类型：
--
作者：
He, Hai-Yan;Tang, Man-Cheng;Tang, Gong-Li
模块化聚酮脱氢酶（PKS）是已知的利用酮合酶（KS）驱动的碳-碳键形成、脱氢酶介导的脱水以形成双键、以及通过硫酯酶（TE）释放产物的酶，所有这些都被认为是大多数聚酮生物合成的“典型”作用。FR 901464是由一个复杂的无酰基转移酶的PKS系统生物合成的，该系统包括一个非末端TE结构域和几个突变的KS结构域。在这里，我们证明这种TE催化聚酮中间体的脱水以产生顺式双键，并且突变的KS将仅具有顺式双键的新生聚酮链转移到下游酰基载体蛋白。这些研究结果不仅提供了新的见解PKS结构域的不同酶功能，但也建议在聚酮装配线的顺式双键形成的替代策略。
Modular polyketide synthases (PKSs) are well known to use ketosynthase (KS)-driven carbon-carbon bond formation, dehydratase-mediated dehydration to form double bonds, and product release by thioesterase (TE), all of which are regarded as the "canonical" roles for most polyketide biosyntheses. FR901464 is biosynthesized by a complex acyltransferase-less PKS system involving a nonterminal TE domain and several mutated KS domains. Here we demonstrate that this TE catalyzes the dehydration of the polyketide intermediate to yield a cis-double bond and a mutated KS transfers the nascent polyketide chain with only a cis-double bond to the downstream acyl carrier protein. These findings not only provide new insights into different enzymatic functions of PKS domains but also suggest an alternative strategy for cis-double bond formation during the polyketide assembly line.