# On the Origin of the Red-Shifted Flavin Absorption Spectra in Fatty Acid Photodecarboxylase

## TL;DR

This paper explains why the flavin in fatty acid photodecarboxylase absorbs light at a longer wavelength than usual, using a combination of quantum and molecular simulations.

## Contribution

The study reveals that the red shift in FAD absorption is mainly due to electrostatic effects from the protein, not structural bending.

## Key findings

- The red shift in FAD absorption is primarily caused by the electrostatic environment of the protein matrix.
- The formation of the red-shifted intermediate FADRS is linked to a stable interaction between the flavin ring and bicarbonate.
- Bending of the FAD structure has a minor effect on the absorption spectrum.

## Abstract

Fatty acid photodecarboxylase
(FAP) is one of the few
known natural
photoenzymes and has attracted considerable interest due to its ability
to convert fatty acids into hydrocarbons upon photoexcitation of its
oxidized flavin adenine dinucleotide (FAD) cofactor. Notably, FAD
in FAP exhibits an absorption spectrum red-shifted by approximately
10–15 nm compared to many other flavoproteins. This shift might
arise from the specific electrostatics of the binding pocket and/or
the slightly bent conformation of the FAD, as suggested by the crystallographic
data. During the photocycle, an even more red-shifted intermediate
(FADRS) has been observed, which ultimately reverts to
the original state. In this work, we simulate the absorption spectrum
of FAD inside FAP using a hybrid computational approach that combines
quantum mechanics (QM) and molecular dynamics (MD) simulations in
the Perturbed Matrix Method (PMM) framework. The computed absorption
spectrum matches and explains the experimental one, not only validating
the effectiveness of the MD-PMM approach but also revealing that the
observed red shift primarily originates from the electrostatic environment
provided by the protein matrix, whereas the effect of bending is comparatively
minor. Additionally, we show that the formation of FAD
RS
is unrelated to changes in active-site residue
protonation or FAD conformation, but instead is likely to arise from
a stable interaction between the flavin ring and bicarbonate, one
of the proposed reaction products.