Different Behaviors of a Substrate in P450 Decarboxylase and Hydroxylase Reveal Reactivity-Enabling Actors
- National Renewable Energy Lab. (NREL), Golden, CO (United States). Biosciences Center
- National Renewable Energy Lab. (NREL), Golden, CO (United States). National Bioenergy Center
Biological routes to the production of fuels from renewable feedstocks hold significant promise in our efforts towards a sustainable future. The fatty acid decarboxylase enzyme (OleTJE) is a cytochrome P450 enzyme that converts long and medium chain fatty acids to terminal alkenes and shares significant similarities in terms of structure, substrate scope and mechanism with the hydroxylase cytochrome P450 (P450BSβ). Recent reports have demonstrated that catalytic pathways in these enzymes bifurcate when the heme is in its iron-hydroxo (compound II) state. In spite of significant similarities, the fundamental underpinnings of their different characteristic wild-type reactivities remain ambiguous. In this work, we develop point charges, modified parameters and report molecular simulations of this crucial intermediate step. Water occupancies and substrate mobility at the active site are observed to be vital differentiating aspects between the two enzymes in the compound II state and corroborate recent experimental hypotheses. Apart from increased substrate mobility in the hydroxylase, which could have implications for enabling the rebound mechanism for hydroxylation, OleTJE is characterized by much stronger binding of the substrate carboxylate group to the active site arginine, implicating it as an important enabling actor for decarboxylation.
- Research Organization:
- National Renewable Energy Laboratory (NREL), Golden, CO (United States)
- Sponsoring Organization:
- USDOE Office of Energy Efficiency and Renewable Energy (EERE), Sustainable Transportation Office. Bioenergy Technologies Office (BETO); USDOE Laboratory Directed Research and Development (LDRD) Program
- Grant/Contract Number:
- AC36-08GO28308
- OSTI ID:
- 1470966
- Report Number(s):
- NREL/JA-2700-72223
- Journal Information:
- Scientific Reports, Vol. 8, Issue 1; ISSN 2045-2322
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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