Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein-Linked Extender Units in Ansamitocin Biosynthesis.,ChemBioChem

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Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein-Linked Extender Units in Ansamitocin Biosynthesis.
ChemBioChem ( IF 2.6 ) Pub Date : 2020-01-10 , DOI: 10.1002/cbic.201900628
Fa Zhang ₁ , Huining Ji ₁ , Imtiaz Ali ₁ , Zixin Deng ₁ , Linquan Bai ₁ , Jianting Zheng ₁

Affiliation

A few acyltransferase (AT) domains of modular polyketide synthases (PKSs) recruit acyl carrier protein (ACP)-linked extender units with unusual C2 substituents to confer functionalities that are not available in coenzyme A (CoA)-linked ones. In this study, an AT specific for methoxymalonyl (MOM)-ACP in the third module of the ansamitocin PKS was structurally and biochemically characterized. The AT uses a conserved tryptophan residue at the entrance of the substrate binding tunnel to discriminate between different carriers. A W275R mutation switches its carrier specificity from the ACP to the CoA molecule. The acyl-AT complex structures clearly show that the MOM-ACP accepted by the AT has the 2S instead of the opposite 2R stereochemistry that is predicted according to the biosynthetic derivation from a d-glycolytic intermediate. Together, these results reveal the structural basis of ATs recognizing ACP-linked extender units in polyketide biosynthesis.

中文翻译：

结构和生化方面的洞察力：安托霉素生物合成中酰基载体蛋白连接的延伸单元的募集。

模块化聚酮化合物合酶（PKS）的一些酰基转移酶（AT）域募集具有不常见C2取代基的酰基载体蛋白（ACP）连接的扩展单元，以赋予在辅酶A（CoA）连接中不可用的功能。在这项研究中，在结构上和生化上对安他霉素PKS第三模块中的甲氧基丙二酰（MOM）-ACP特有的AT进行了表征。AT在底物结合通道的入口使用保守的色氨酸残基来区分不同的载体。W275R突变将其载体特异性从ACP切换到CoA分子。酰基-AT复合物结构清楚地表明，AT接受的MOM-ACP具有2S而不是相反的2R立体化学，根据从d-糖酵解中间体的生物合成推导，该化学是预测的。一起，

更新日期：2020-01-10

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