聚酮化合物β-酮酰-ACP合酶的计算机对比分析与组合生物合成  

Comparison and Analysis of β-ketoacyl-ACP Synthase from Polyketide with Computer and Its Implication on Combinatorial Biosynthesis

作　　者：唐滢[1] 夏立秋[1] 王海龙[1] 胡胜标[1] 余子全[1] 孙运军[1] 

机构地区：[1]湖南师范大学生命科学学院微生物分子生物学湖南省重点实验室,湖南长沙410081

出　　处：《微生物学通报》2010年第2期191-198,共8页Microbiology China

基　　金：国家863计划项目(No.2006AA02Z187);国家自然科学基金项目(No.30870064);教育部博士点基金项目(No.20060542006)

摘　　要：为了合理地设计新的聚酮化合物提高组合生物合成的效率,本文使用ClustalW、Mega4.0分析了26种来自不同聚酮合酶的β-酮酰-ACP合酶结构域的序列特征,并用ProtParam、Phdsec、Swiss-Model等工具对其中9种具有不同底物专一性的β-酮酰-ACP合酶的一级结构、二级结构和三级结构及活性位点进行了分析与预测。发现它们结构上的相似性大于序列上的相似性;活性位点都富含丝氨酸;底物含有2个羧酸基团的β-酮酰-ACP合酶的理论pI均小于5.0且其形式电荷总量也偏低;序列V303ELHGTGTPLGDPIEAGA320是这26种β-酮酰-ACP合酶的一段保守序列,但它并不与活性位点相邻。这些研究对进行聚酮合酶的模块或结构域替换以及定点突变具有重要的指导意义,也为探讨其的进化机制提供了参考。For rational design of novel polyketides and improving the combinatorial biosynthesis of polyketides. 26 β-ketoacyl-ACP synthases from several polyketide synthases were analysed with ClustalW, MEGA4.0. The primary parameters, secondary, tertiary structures and active sites of nine of them with different substrate specificity were compared or predicted in detail using ProtParam, Phdsec, Swiss-Model. The results revealed that they have more similarity in structure than in sequence and all own a high percentage of serine in their active sites; in addition, the β-ketoacyl-ACP synthases whose substrates possess two carboxyl groups were found to have a theoretical pI less than 5.0, and their formal charges sum were on the low side too; the conserved sequence of the 26 13-ketoacyl-ACP synthases is V^303 ELHGTGTPLGDPIEAGA^320, but it is away from the active site. These conclusions have promising potential for module or domain substitution and site-specific mutation ofpolyketide synthases; also providing a reference for the study of their evolution mechanism.

关 键 词：聚酮化合物 β-酮酰-ACP合酶 组合生物合成 底物专一性 

分 类 号：Q55[生物学—生物化学]