Flavin mononucleotide , biosynthesis

The oxidation state of thiazolines and oxazolines can be adjusted by additional tailoring enzymes. For instance, oxidation domains (Ox) composed of approximately 250 amino acids utilize the cofactor FMN (flavin mononucleotide) to form aromatic oxazoles and thiazoles from oxazolines and thiazolines, respectively. Such domains are likely utilized in the biosynthesis of the disorazoles, " diazonimides, bleomycin, and epothiolone. The typical domain organization for a synthetase containing an oxidation domain is Cy-A-PCP-Ox however, in myxothiazol biosynthesis one oxidation domain is incorporated into an A domain. Alternatively, NRPSs can utilize NAD(P)H reductase domains to convert thiazolines and oxazolines into thiazolidines and oxazolidines, respectively. For instance, PchC is a reductase domain from the pyochelin biosynthetic pathway that acts in trans to reduce a thiazolyinyl-Y-PCP-bound intermediate to the corresponding thiazolidynyl-Y-PCP. ... 

Riboflavin (vitamin Bj) is chemically specified as a 7,8-dimethyl-10-(T-D-ribityl) isoalloxazine (Eignre 19.22). It is a precnrsor of certain essential coenzymes, such as flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD) in these forms vitamin Bj is involved in redox reactions, such as hydroxylations, oxidative carboxylations, dioxygenations, and the reduction of oxygen to hydrogen peroxide. It is also involved in the biosynthesis of niacin-containing coenzymes from tryptophan. 

Structure and biosynthesis of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)... 

In higher mammals, riboflavin is absorbed readily from the intestines and distributed to all tis.sues. It is the precursor in the biosynthesis of the cocnzyme.s flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The metabolic functions of this vitamin involve these Iwocoenzymes. which participate in numerous vital oxidation-reduction proces.ses. FMN (riboflavin 5 -phosphate) is produced from the vitamin and ATP by flavokinasc catalysis. This step con be inhibited by phcnothiazincs and the tricyclic antidepressants. FAD originates from an FMN and ATP reaction that involves reversible dinucicotide formation catalyzed by flavin nucleotide pyrophosphorylase. The.se coenzymes function in combination with several enzymes as coenzyme-en-zyme complexes, often characterized as, flavoproteins. 

It is still unknown how the pyrimidine intermediate 5 is dephosphorylated (reaction VI). However, it is well established that the dephosphorylation product 6 is condensed with 3,4-dihydroxy-2-butanone 4-phosphate (8) by the catalytic action of lumazine synthase (reaction VIII). The carbohydrate substrate 8 is in turn obtained from ribulose phosphate (7) by a complex reaction sequence that is catalyzed by a single enzyme, 3,4-dihydroxy-2-butanone 4-phosphate synthase (reaction VII). As mentioned above, the lumazine 9 is converted to riboflavin (10) by the catalytic action of riboflavin synthase (reaction IX). Ultimately, riboflavin is converted to the coenzymes, riboflavin 5 -phosphate (flavin mononucleotide (FMN), 11) and flavin adenine dinucleotide (FAD, 12) by the catalytic action of riboflavin kinase (reaction X) and FAD synthase (reaction XI). These reaction steps are required in all organisms, irrespective of their acquisition of riboflavin from nutritional sources or by endogenous biosynthesis. 

Several strategies to increase the production of electron shuttles have been developed to improve the MFC performance in the model exoeleetrogens. For Shewanella species, flavins (riboflavin and flavin mononucleotide) are the most well-known self-secreted electron shuttles. Using deletion mutants lacking various Mtr-associated proteins, the significance of the Mtr extracellular respiratory pathway for the reduction of flavins has been demonstrated. The decaheme cytochromes found on the outer surface of the cell (MtrC and OmcA) are required for the majority of Mtr-associated proteins activity. Weakly acidic pH resulted in poor performance of the MFC and low riboflavin concentrations in the bacterial cultures, while enhanced electrochemical activity of riboflavin was reported at alkaline pH. The increase of riboflavin biosynthesis by Shewanella at the alkaline condition underlies the improvement in the electricity output in MFCs. ... 

STEP 7 OF FIGURE 25.1 OXIDATION The final step in PLP biosynthesis is oxidation of the primary alcohol group in pyridoxine 5 -phosphate to the corresponding aldehyde. Typically, as we ve seen on numerous occasions, alcohol oxidations are carried out hy either NAD" " or NADP+. In this instance, however, flavin mononucleotide (FMN) is involved as the oxidizing coenzyme and reduced flavin mononucleotide (FMNH2) is the hy-product. The details of the reaction are not clear, but evidence suggests that a hydride transfer is involved, just as in NAD" " oxidations. 

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