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International Journal of Molecular... May 2023This short review reports the surprising phenomenon of nuclear hyperpolarization occurring in chemical reactions, which is called CIDNP (chemically induced dynamic... (Review)
Review
This short review reports the surprising phenomenon of nuclear hyperpolarization occurring in chemical reactions, which is called CIDNP (chemically induced dynamic nuclear polarization) or photo-CIDNP if the chemical reaction is light-driven. The phenomenon occurs in both liquid and solid-state, and electron transfer systems, often carrying flavins as electron acceptors, are involved. Here, we explain the physical and chemical properties of flavins, their occurrence in spin-correlated radical pairs (SCRP) and the possible involvement of flavin-carrying SCRPs in animal magneto-reception at earth's magnetic field.
Topics: Animals; Flavoproteins; Magnetic Fields; Electron Transport; Flavins
PubMed: 37175925
DOI: 10.3390/ijms24098218 -
Chembiochem : a European Journal of... Jun 2022Methods for facile site-selective modifications of proteins are in high demand. We have recently shown that a flavin transferase can be used for site-specific covalent...
Methods for facile site-selective modifications of proteins are in high demand. We have recently shown that a flavin transferase can be used for site-specific covalent attachment of a chromo- and fluorogenic flavin (FMN) to any targeted protein. Although this Flavin-tag method resulted in efficient labeling of proteins in vitro, labelling in E. coli cells resulted in partial flavin incorporation. It was also restricted in the type of installed label with only one type of flavin, FMN, being incorporated. Here, we report on an extension of the Flavin-tag method that addresses previous limitations. We demonstrate that co-expression of FAD synthetase improves the flavin incorporation efficiency, allowing complete flavin-labeling of a target protein in E. coli cells. Furthermore, we have found that various flavin derivatives and even a nicotinamide can be covalently attached to a target protein, rendering this method even more versatile and valuable.
Topics: Escherichia coli; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Flavins; Proteins; Transferases
PubMed: 35373879
DOI: 10.1002/cbic.202200144 -
The FEBS Journal May 2023The UbiX/UbiD system is widespread in microbes and responsible for the reversible decarboxylation of unsaturated carboxylic acids. The UbiD enzyme catalyzes this unusual... (Review)
Review
The UbiX/UbiD system is widespread in microbes and responsible for the reversible decarboxylation of unsaturated carboxylic acids. The UbiD enzyme catalyzes this unusual reaction using a prenylated flavin (prFMN) as cofactor, the latter formed by the flavin prenyltransferase UbiX. A detailed picture of the biochemistry of flavin prenylation, oxidative maturation, and covalent catalysis underpinning reversible decarboxylation is emerging. This reveals the prFMN cofactor can undergo a wide range of transformations, complemented by considerable UbiD-variability. These provide a blueprint for biotechnological applications aimed at producing hydrocarbons or aromatic C-H activation through carboxylation.
Topics: Flavins; Carboxy-Lyases; Flavin Mononucleotide; Oxidation-Reduction; Dimethylallyltranstransferase
PubMed: 35073609
DOI: 10.1111/febs.16371 -
Current Opinion in Structural Biology Aug 2022The ubiquitous UbiX-UbiD system is associated with a wide range of microbial (de)carboxylation reactions. Recent X-ray crystallographic studies have contributed to... (Review)
Review
The ubiquitous UbiX-UbiD system is associated with a wide range of microbial (de)carboxylation reactions. Recent X-ray crystallographic studies have contributed to elucidating the enigmatic mechanism underpinning the conversion of α,β-unsaturated acids by this system. The UbiD component utilises a unique cofactor, prenylated flavin (prFMN), generated by the bespoke action of the associated UbiX flavin prenyltransferase. Structure determination of a range of UbiX/UbiD representatives has revealed a generic mode of action for both the flavin-to-prFMN metamorphosis and the (de)carboxylation. In contrast to the conserved UbiX, the UbiD superfamily is associated with a versatile substrate range. The latter is reflected in the considerable variety of UbiD quaternary structure, dynamic behaviour and active site architecture. Directed evolution of UbiD enzymes has taken advantage of this apparent malleability to generate new variants supporting in vivo hydrocarbon production. Other applications include coupling UbiD to carboxylic acid reductase to convert alkenes into α,β-unsaturated aldehydes via enzymatic CO fixation.
Topics: Aspergillus niger; Carboxy-Lyases; Decarboxylation; Flavins; Prenylation
PubMed: 35843126
DOI: 10.1016/j.sbi.2022.102432 -
IUBMB Life Jul 2022The flavin mononucleotide (FMN) cofactor of respiratory complex I occupies a key position in the electron transport chain. Here, the electrons coming from NADH start the... (Review)
Review
The flavin mononucleotide (FMN) cofactor of respiratory complex I occupies a key position in the electron transport chain. Here, the electrons coming from NADH start the sequence of oxidoreduction reactions, which drives the generation of the proton-motive force necessary for ATP synthesis. The overall architecture and the general catalytic proprieties of the FMN site are mostly well established. However, several aspects regarding the complex I flavin cofactor are still unknown. For example, the flavin binding to the N-module, the NADH-oxidizing portion of complex I, lacks a molecular description. The dissociation of FMN from the enzyme is beginning to emerge as an important regulatory mechanism of complex I activity and ROS production. Finally, how mitochondria import and metabolize FMN is still uncertain. This review summarizes the current knowledge on complex I flavin cofactor and discusses the open questions for future research.
Topics: Electron Transport Complex I; Flavin Mononucleotide; Flavins; NAD; Oxidation-Reduction
PubMed: 35166025
DOI: 10.1002/iub.2600 -
International Journal of Molecular... Feb 2022Natural products are usually highly complicated organic molecules with special scaffolds, and they are an important resource in medicine. Natural products with... (Review)
Review
Natural products are usually highly complicated organic molecules with special scaffolds, and they are an important resource in medicine. Natural products with complicated structures are produced by enzymes, and this is still a challenging research field, its mechanisms requiring detailed methods for elucidation. Flavin adenine dinucleotide (FAD)-dependent monooxygenases (FMOs) catalyze many oxidation reactions with chemo-, regio-, and stereo-selectivity, and they are involved in the synthesis of many natural products. In this review, we introduce the mechanisms for different FMOs, with the classical FAD (C4a)-hydroperoxide as the major oxidant. We also summarize the difference between FMOs and cytochrome P450 (CYP450) monooxygenases emphasizing the advantages of FMOs and their specificity for substrates. Finally, we present examples of FMO-catalyzed synthesis of natural products. Based on these explanations, this review will expand our knowledge of FMOs as powerful enzymes, as well as implementation of the FMOs as effective tools for biosynthesis.
Topics: Biological Products; Cytochrome P-450 Enzyme System; Dinitrocresols; Flavin-Adenine Dinucleotide; Flavins; Oxygenases
PubMed: 35269764
DOI: 10.3390/ijms23052622 -
Current Opinion in Chemical Biology Dec 2018Prenylated flavin (prFMN) is a recently discovered cofactor that underpins catalysis in the ubiquitous microbial UbiDX system. UbiX acts as a flavin prenyltransferase... (Review)
Review
Prenylated flavin (prFMN) is a recently discovered cofactor that underpins catalysis in the ubiquitous microbial UbiDX system. UbiX acts as a flavin prenyltransferase while UbiD is a prFMN-dependent reversible (de)carboxylase. The extensive modification of flavin by prenylation, and the consecutive oxidation to the prFMN azomethine ylide, leads to cofactor metamorphosis. While prFMN is no longer able to perform N5-based classical flavin chemistry, it is capable of forming cycloadducts with dipolarophiles, long-lived C4a-based radical species as well as undergoing extensive light driven isomerization. An ever-expanding range of distinct prFMN forms hints at the possibility of novel prFMN driven biochemistry yet to be discovered.
Topics: Aspergillus niger; Carboxy-Lyases; Escherichia coli; Flavins; Models, Molecular; Oxidation-Reduction; Prenylation; Pseudomonas aeruginosa
PubMed: 30326424
DOI: 10.1016/j.cbpa.2018.09.024 -
Current Opinion in Structural Biology Dec 2022Photoenzymes use light to initiate biochemical reactions. Although rarely found in nature, their study has advanced understanding of how light energy can be harnessed to... (Review)
Review
Photoenzymes use light to initiate biochemical reactions. Although rarely found in nature, their study has advanced understanding of how light energy can be harnessed to facilitate enzyme catalysis, which is also of importance to the design and engineering of man-made photocatalysts. Natural photoenzymes can be assigned to one of two families, based broadly on the nature of the light-sensing chromophores used, those being chlorophyll-like tetrapyrroles or flavins. In all cases, light absorption leads to excited state electron transfer, which in turn initiates photocatalysis. Reviewed here are recent findings relating to the structures and mechanisms of known photoenzymes. We highlight recent advances that have deepened understanding of mechanisms in biological photocatalysis.
Topics: Humans; Catalysis; Flavins
PubMed: 36323132
DOI: 10.1016/j.sbi.2022.102491 -
Phytochemistry Sep 2021Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are utilized as coenzymes in many biochemical reduction-oxidation reactions owing to the ability of the... (Review)
Review
Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are utilized as coenzymes in many biochemical reduction-oxidation reactions owing to the ability of the tricyclic isoalloxazine ring system to employ the oxidized, radical and reduced state. We have analyzed the genome of Arabidopsis thaliana to establish an inventory of genes encoding flavin-dependent enzymes (flavoenzymes) as a basis to explore the range of flavin-dependent biochemical reactions that occur in this model plant. Expectedly, flavoenzymes catalyze many pivotal reactions in primary catabolism, which are connected to the degradation of basic metabolites, such as fatty and amino acids as well as carbohydrates and purines. On the other hand, flavoenzymes play diverse roles in anabolic reactions most notably the biosynthesis of amino acids as well as the biosynthesis of pyrimidines and sterols. Importantly, the role of flavoenzymes goes much beyond these basic reactions and extends into pathways that are equally crucial for plant life, for example the production of natural products. In this context, we outline the participation of flavoenzymes in the biosynthesis and maintenance of cofactors, coenzymes and accessory plant pigments (e. g. carotenoids) as well as phytohormones. Moreover, several multigene families have emerged as important components of plant immunity, for example the family of berberine bridge enzyme-like enzymes, flavin-dependent monooxygenases and NADPH oxidases. Furthermore, the versatility of flavoenzymes is highlighted by their role in reactions leading to tRNA-modifications, chromatin regulation and cellular redox homeostasis. The favorable photochemical properties of the flavin chromophore are exploited by photoreceptors to govern crucial processes of plant adaptation and development. Finally, a sequence- and structure-based approach was undertaken to gain insight into the catalytic role of uncharacterized flavoenzymes indicating their involvement in unknown biochemical reactions and pathways in A. thaliana.
Topics: Arabidopsis; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Flavins; Oxidation-Reduction
PubMed: 34118767
DOI: 10.1016/j.phytochem.2021.112822 -
Current Opinion in Chemical Biology Apr 2016Ever since the discovery of the flavin cofactor more than 80 years ago, flavin-dependent enzymes have emerged as ubiquitous and versatile redox catalysts in primary... (Review)
Review
Ever since the discovery of the flavin cofactor more than 80 years ago, flavin-dependent enzymes have emerged as ubiquitous and versatile redox catalysts in primary metabolism. Yet, the recent advances in the discovery and characterization of secondary metabolic pathways exposed new roles for flavin-mediated catalysis in the generation of structurally complex natural products. Here, we review a selection of key biosynthetic flavoenzymes from marine bacterial secondary metabolism and illustrate how their functional and mechanistic investigation expanded our view of the cofactor's chemical repertoire and led to the discovery of a previously unknown flavin redox state.
Topics: Bacteria; Catalysis; Enzymes; Flavins; Marine Biology; Oxidation-Reduction
PubMed: 26803009
DOI: 10.1016/j.cbpa.2016.01.001