Computational Evidence for the Enzymatic Transformation of 2‑Hydroxypropylphosphonate to Methylphosphonate
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Abstract
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<sup>–1</sup>, 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