Abstract
The functional diversity of flavin enzymes is astonishing, reflecting the chemical versatility of the flavin coenzyme. With around 1 % of the genome encoding flavoproteins, flavins are at the heart of a plethora of reactions impacting all areas of biology [1]. Generations of enzymologists have marveled at the astonishing diversity of reactions catalyzed by flavoenzymes, most of them dependent on redox chemistry, such as dehydrogenation, oxidation, monooxygenation, halogenation and reduction reactions (e.g. disulfides and various types of double bond) [2]. Since the discovery of the first flavin-containing enzyme by Otto Warburg in the 1930s [3], the number of " yellow " enzymes has steadily increased over the last 20-30 years, due to advances in molecular cloning and genome sequencing[1]. In this sense, the field of flavoenzymology has recently undergone a radical change, with the discovery of a series of enzymes which, although chemically and biologically diverse, share a common feature : they function through the formation of intermediates that involve a covalent flavin[4, 5]. Their discovery has rekindled interest in flavoenzyme mechanisms, revealing new paradigms and concepts in flavin chemistry and enzymology. Their roles in cellular metabolism, the possibility of exploiting them as targets for mechanism-based inhibitors and their potential in biocatalysis remain to be discovered and explored for the most part. This seminar will provide an opportunity to present our recent findings on enzymes involved in nucleotide and nucleoside metabolism and operating with covalent chemistry " flavinic "[6, 7, 8]. The existence of these types of reaction must now be considered, for example, in the characterization of metabolic and biosynthetic pathways involving putative flavoproteins, or when enzymes are sought to carry out biotransformations of biotechnological importance. Thus, non-canonical covalent reactions by flavins are emerging as a new concept in enzymology and fundamental biochemistry.
References
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