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Fundamental Processes in Flavoprotein Photochemistry

Abstract : Flavins are derivatives of vitamin B2 that form a highly versatile group of chromophores found in a large variety of enzymes and photoreceptor proteins. They can adopt three different redox states with various protonation states, leading to at least five physiologically relevant forms, with distinct electronic absorption spectra. Despite the diverse photophysical properties of the flavin cofactors, there are only very few natural photo-responsive flavoproteins. The vast majority of flavoproteins perform non-light-driven physiological functions (“non-photoactive”), although ultrafast, reversible photoinduced redox reactions between flavins and surrounding residues still widely occur in these systems, which can be viewed as photo-protective “self-quenching”. The past few decades have seen a blooming in the study of flavoproteins for their photocatalytic and photo-biotechnological applications. Moreover, a newly emerging approach in the development of novel photocatalysts from canonical “non-photoactive” flavoenzymes is making use of the photochemistry of reduced flavins instead of the oxidized resting state. Furthermore, practical implications of photochemistry of yet different flavin species are envisaged, but a basic understanding of their mechanisms is still required. In this thesis, applying ultrafast absorption and fluorescence spectroscopy combined with molecular simulations and quantum chemistry approaches, a variety of fundamental photochemical processes in flavoproteins is investigated. First the photoreduction of oxidized flavins was revisited in a flavoprotein, ferredoxin-NADP+ oxidoreductase (FNR), with closely packed reactant configurations, allowing ultrafast formation of intermediate radical pairs. Combining experimental and modeling techniques allowed a detailed assessment of the influence of the environment on the spectral properties of both the anionic flavin and the cationic amino acid (tyrosine or tryptophan) radicals. We further investigated the photochemistry of protein-bound flavin species in different chemical states that are largely unexplored in the literature. It is demonstrated that photooxidation of anionic flavin radicals, which act as reaction intermediates in many biochemical reactions, efficiently occurs within ~100 fs in several flavoprotein oxidases. This process, effectively the reverse of the well-known photoreduction of oxidized flavin may constitute a universal decay pathway. The excited-state properties of fully reduced flavins were studied in several FNR systems where they are involved as functional intermediates, and compared with those in solution. Valuable information concerning their electronic structures and the flavin flexibility was obtained and compared with atomic simulations, with important catalytic implications. Finally, an unprecedented photo-dissociation phenomenon was revealed for a non-covalent charge transfer complex of flavin and a inhibitor in the flavoenzyme monomeric sarcosine oxidase. This process occurs on the timescale of a few hundred femtoseconds and can be attributed to a well-defined photoinduced isomerization of the inhibitor. Altogether, the described findings, which include the discovery of two hitherto undocumented photochemical processes in flavoproteins, expand the repertoire of photochemistry involving flavin cofactors. This work may open new avenues for the exploration of flavin photochemistry with ultimately possible practical implications as novel photocatalysts and optogenetic tools.
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Submitted on : Tuesday, September 27, 2022 - 3:38:46 PM
Last modification on : Wednesday, September 28, 2022 - 2:19:42 PM


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  • HAL Id : tel-03789651, version 1



Bo Zhuang. Fundamental Processes in Flavoprotein Photochemistry. Biological Physics []. Institut Polytechnique de Paris, 2022. English. ⟨NNT : 2022IPPAX051⟩. ⟨tel-03789651⟩



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