对迭代型高度还原聚酮合酶功能域的编程进行重新设计。
Reengineering the programming of a functional domain of an iterative highly reducing polyketide synthase.
作者信息
Piech Oliver, Cox Russell J
机构信息
Institute for Organic Chemistry, Leibniz University of Hannover Schneiderberg 1B 30167 Hannover Germany
BMWZ, Leibniz University of Hannover Schneiderberg 38 30167 Hannover Germany.
出版信息
RSC Adv. 2020 May 15;10(31):18469-18476. doi: 10.1039/d0ra04026f. eCollection 2020 May 10.
A structural model of the enoyl reductase (ER) catalytic domain of the fungal highly-reducing polyketide synthase squalestatin tetraketide synthase (SQTKS) was developed. Simulated docking of substrates and inhibitors allowed the definition of active site residues involved in catalysis and substrate selectivity. These were investigated with the aim of extending the substrate scope. Residues were identified which limit the substrate selectivity of the SQTKS ER, and these were mutated and the engineered ER domain assayed . Significant changes to the programming of the mutant SQTKS ER domains were observed allowing the processing of longer and more methylated substrates.
构建了真菌高还原型聚酮合酶角鲨烯他汀四酮合酶（SQTKS）的烯酰还原酶（ER）催化结构域的结构模型。通过对底物和抑制剂进行模拟对接，确定了参与催化和底物选择性的活性位点残基。为了扩大底物范围对这些残基进行了研究。鉴定出了限制SQTKS ER底物选择性的残基，并对这些残基进行了突变，然后对工程化的ER结构域进行了检测。观察到突变型SQTKS ER结构域的程序设计有显著变化，能够处理更长且甲基化程度更高的底物。
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