Rational engineering of amide synthetase enables bioconversion to diverse xiamenmycin derivatives
Rational engineering of amide synthetase enables bioconversion to diverse xiamenmycin derivatives
复制标题
酰胺合成酶的合理工程能够生物转化为多种厦门霉素衍生物
DOI：
10.1039/c9cc07826f
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发表时间：
2019
影响因子：
4.9
通讯作者：
Min-Juan Xu
中科院分区：
文献类型：
--
作者：
Jing-Yi Weng;Xu-Liang Bu;Bei-Bei He;Zhuo Cheng;Jun Xu;Lin-Tai Da;Min-Juan Xu
XimA是一种独特的酰胺合成酶，属于腺苷酸化酶的ANL超家族，但具有特殊的结构折叠。为了改善酶的混杂性，我们在XimA的理论模型的基础上，在特定位置通过定点突变来工程化XimA。因此，我们能够产生不同的苯并吡喃衍生物与多达15个不同的L-型和D-型氨基酸取代，催化的几个XimA变体。分子对接和分子动力学模拟进行了各种XimA系统提供了进一步的结构洞察苯丙氨酸-201作为蛋白质动力学和酶催化的活性位点残基的取代效果。
XimA is a unique amide synthetase that belongs to the ANL superfamily of adenylating enzymes, but with a special structural fold. In order to improve the enzyme promiscuity, we engineered XimA by site-directed mutagenesis at a specific position based on our theoretical model of XimA. Thus, we were able to produce diverse benzopyran derivatives with up to 15 different L-form and D-form amino acid substitutions, catalyzed by several XimA variants. Molecular docking and molecular dynamics simulations conducted for various XimA systems provide further structural insights into the substitution effects of the phenylalanine-201 as an active site residue on protein dynamics and enzyme catalysis.