Cytochrome P450 monooxygenases (P450s) play important roles in herbicide resistance. In this study, there are four amino acid mutations (F39Y, H163Y, S203A, and V361E) between CYP96A146-S and CYP96A146-R, which were cloned, respectively, from susceptible (S) and tribenuron-methyl-resistant (TR) Descurainia sophia. The Arabidopsis expressing CYP96A146-S or CYP96A146-R showed resistance to tribenuron-methyl, carfentrazone-ethyl, and oxyfluorfen, while Arabidopsis transformed with CYP96A146-R or CYP96A146 with any two or three mutations of H163Y, S203A, or V361E exhibited significantly higher resistance to tribenuron-methyl than Arabidopsis expressing CYP96A146-S. The metabolic rates of tribenuron-methyl were significantly faster in Arabidopsis expressing CYP96A146-R than that with CYP96A146-S. The molecular dynamics simulation demonstrated that amino acid mutations did not affect the domain of the HEM ring, which could significantly enhance the volume of the catalytic pocket in P450 (CYP96A146), thereby increasing the collision rate between the catalytic pocket and tribenuron-methyl. Hence, the amino acid mutations may be one of the mechanisms underlying P450-mediated herbicide resistance.

中文翻译：

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Descurainia sophia 细胞色素 P450 （CYP96A146） 氨基酸突变对甲基三苯磺隆代谢和耐药性的影响


细胞色素 P450 单加氧酶 （P450） 在除草剂抗性中起重要作用。在这项研究中，CYP96A146-S 和 CYP96A146-R 之间存在 4 个氨基酸突变 （F39Y、H163Y、S203A 和 V361E），它们分别是从易感 （S） 和甲基三苯磺酸钠耐药 （TR） Descurainia sophia 克隆而来的。表达 CYP96A146-S 或 CYP96A146-R 的拟南芥对甲基三苯磺隆、卡芬草酮乙酯和氧氟醚表现出耐药性，而用 CYP96A146-R 或CYP96A146转化的拟南芥具有 H163Y、S203A 或 V361E 的任意两个或三个突变，对甲基三苯磺酸钠的耐药性显著高于表达 CYP96A146-S 的拟南芥。在表达 CYP96A146-R 的拟南芥中甲基三苯磺隆的代谢速率显著快于 CYP96A146-S。分子动力学模拟表明，氨基酸突变不会影响 HEM 环的结构域，可显著提高 P450 （CYP96A146） 中催化口袋的体积，从而提高催化口袋与甲基三苯磺隆之间的碰撞速率。因此，氨基酸突变可能是 P450 介导的除草剂抗性机制之一。