Understanding the origins of greenhouse gas methane in the ocean is of great environmental importance, especially for global climate change and the flow of carbon within the earth surface system. A mutant (E176H) of 2-hydroxyethylphosphonate dioxygenase (HEPD) has been reported to catalyze the transformation of 2-hydroxypropylphosphonate (2-HEP) to methylphosphonate (MPn), a compound that can be easily transformed to methane by C–P lyase in a marine microbe. Here, the HEPD E176H-catalyzed transformation of 2-HEP to MPn was investigated at the molecular level using the quantum mechanics/molecular mechanics method. The results evidenced the feasibility of the transformation of 2-HEP to MPn and highlighted that the transformation contains five elementary steps: H abstraction, O–O bond cleavage, H transfer, C–C bond cleavage, and MPn formation. H abstraction was found to be the rate-determining step with an energy barrier of 17.8 kcal/mol, which is in reasonable accordance with the experimentally determined rate constant (0.38 s^–1, corresponding to 18.0 kcal/mol). Three intersystem crossing events were involved in H-abstraction, H-transfer, and MPn-formation steps. Residue electrostatic analysis on the rate-determining step suggests that proper mutation of Tyr174 may improve the enzymatic efficiency.

中文翻译：

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2-羟丙基膦酸酯酶促转化为甲基膦酸酯的计算证据

理解海洋中温室气体甲烷的起源具有重大的环境意义，特别是对于全球气候变化和地表系统中碳的流动而言。据报道，2-羟乙基膦酸酯双加氧酶（HEPD）的突变体（E176H）催化2-羟丙基膦酸酯（2-HEP）转化为甲基膦酸酯（MPn），该化合物可通过C-P裂解酶轻松转化为甲烷。海洋微生物。在这里，使用量子力学/分子力学方法在分子水平上研究了HEPD E176H催化的2-HEP到MPn的转化。结果证明了将2-HEP转化为MPn的可行性，并强调了该转化包含五个基本步骤：H提取，O-O键断裂，H转移，CC键断裂和MPn形成。^–1，对应于18.0 kcal / mol）。H提取，H转移和MPn形成步骤涉及三个系统间交叉事件。速率确定步骤上的残留静电分析表明，Tyr174的适当突变可以提高酶的效率。