A dynamic active-site water molecule drives the photocatalysis in fatty acid photodecarboxylase
- 1Department of Chemistry and Industrial Chemistry
- 2University of Pisa
Abstract
Fatty acid photodecarboxylase (FAP) is a flavin-based photoenzyme that uses blue light to convert fatty acids into hydrocarbons, an attractive platform for sustainable fuel production. Its efficiency is set by a competition between photoinduced electron transfer, productive decarboxylation and unproductive back electron transfer, yet how the protein controls this competition at the atomistic level remains unresolved. Here, by following the coupled evolution of electrons and nuclei in real time with excited-state nonadiabatic dynamics simulations of wild-type FAP and an engineered variant, we show that a single water molecule in the active site acts as a dynamic switch rather than a static element of the hydrogen-bonding network. Rearrangement of its hydrogen bonding from the protein toward the flavin cofactor opens a predominantly adiabatic pathway for electron transfer. The resulting charge-transfer state is stabilized by a coupled protein–solvent response before decaying through competing back electron transfer and decarboxylation. Because electron transfer goes through a specific structural rearrangement, this mechanism cannot be fully captured by standard semiclassical Marcus theory. Our results show that the active-site hydrogenbonding network directly controls photochemical reactivity and indicate that photoenzyme engineering should target dynamic solvent interactions alongside amino acid residues.
Related
- A Single Active-Site Water Molecule Encodes Two Distinct Proton-Coupled Electron Transfer Pathways in Fatty Acid Photodecarboxylase
- Sulfur(VI) Fluoride Exchange (SuFEx)-Enabled synthesis of Aggregation-Induced Emission photosensitizer-active polysulfate network for photocatalysis
- Different Photons, Same Chemistry: Identical Mechanism and Efficiency of Fatty Acid Photodecarboxylase under Blue and UV Excitation
- Adaptive Catalytic Interfaces for Biomass-Derived Model Compounds: Dynamic Active Sites, Microenvironments, and Operando-Guided Design
- Mobilis: an open-source toolkit for charge transport in organic semiconductors, from crystal structures to temperaturedependent mobilities with dynamic disorder and active learning
BibTeX
@misc{sangiogogil2026dynamic,
title = {{A dynamic active-site water molecule drives the photocatalysis in fatty acid photodecarboxylase}},
author = {Eduarda Sangiogo-Gil and Giacomo Londi and Benedetta Mennucci},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008329/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008329/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A dynamic active-site water molecule drives the photocatalysis in fatty acid photodecarboxylase
AU - Eduarda Sangiogo-Gil
AU - Giacomo Londi
AU - Benedetta Mennucci
PY - 2026
DA - 2026/09/04
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008329/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008329/v1
AB - Fatty acid photodecarboxylase (FAP) is a flavin-based photoenzyme that uses blue light to convert fatty acids into hydrocarbons, an attractive platform for sustainable fuel production. Its efficiency is set by a competition between photoinduced electron transfer, productive decarboxylation and unproductive back electron transfer, yet how the protein controls this competition at the atomistic level remains unresolved. Here, by following the coupled evolution of electrons and nuclei in real time with excited-state nonadiabatic dynamics simulations of wild-type FAP and an engineered variant, we show that a single water molecule in the active site acts as a dynamic switch rather than a static element of the hydrogen-bonding network. Rearrangement of its hydrogen bonding from the protein toward the flavin cofactor opens a predominantly adiabatic pathway for electron transfer. The resulting charge-transfer state is stabilized by a coupled protein–solvent response before decaying through competing back electron transfer and decarboxylation. Because electron transfer goes through a specific structural rearrangement, this mechanism cannot be fully captured by standard semiclassical Marcus theory. Our results show that the active-site hydrogenbonding network directly controls photochemical reactivity and indicate that photoenzyme engineering should target dynamic solvent interactions alongside amino acid residues.
ER -