Insights into the stereospecificity of ketoreduction in a modular polyketide synthase
Insights into the stereospecificity of ketoreduction in a modular polyketide synthase
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DOI：
10.1039/c1ob00022e
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Leadlay, Peter F.
中科院分区：
文献类型：
--
作者：
Kwan, David H.;Tosin, Manuela;Leadlay, Peter F.
酮还原酶负责在复杂聚酮化合物天然产物的生物合成期间产生羟基立体中心。分离的聚酮酮还原酶的先前研究已经表明，酮还原的立体特异性可以通过选择的活性位点氨基酸的诱变来切换。我们在这里表明，在完整的聚酮合酶多酶的上下文中，相同的变化不会以相同的方式改变立体化学的结果。这些发现指向其他因素，管理完整的多酶在体内酮还原酶立体特异性。
Ketoreductase enzymes are responsible for the generation of hydroxyl stereocentres during the biosynthesis of complex polyketide natural products. Previous studies of isolated polyketide ketoreductases have shown that the stereospecificity of ketoreduction can be switched by mutagenesis of selected active site amino acids. We show here that in the context of the intact polyketide synthase multienzyme the same changes do not alter the stereochemical outcome in the same way. These findings point towards additional factors that govern ketoreductase stereospecificity on intact multienzymes in vivo.