Riboflavin bacterial synthesis

Dietary deficiency is relatively widespread, yet is apparently never fatal there is not even a clearly characteristic riboflavin deficiency disease. In addition to intestinal bacterial synthesis of the vitamin, there is very efficient conservation and reutilization of riboflavin in tissues. Flavin coenzymes are tightly enzyme bound, in some cases covalently, and control of tissue flavins is largely at the level of synthesis and catabolism of flavin-dependent enzymes. 

Intestinal bacteria synthesize riboflavin, and fecal losses of the vitamin may be five- to six-fold higher than intake. It is possible that bacterial synthesis makes a significant contribution to riboflavin intake, because there is carrier-mediated uptake of riboflavin into colonocytes in culture. The activity of the carrier is increased in riboflavin deficiency and decreased when the cells are cultured in the presence of high concentrations of riboflavin. The same carrier mechanism seems to be involved in tissue uptake of riboflavin (Said et al., 2000). 

When considering sources of niacin, it should be noted that niacin can be, and is, synthesized by the intestinal flora. However, the amount produced is only of minor importance in the human. By contrast, as with thiamin and riboflavin, ruminants (cattle, sheep, etc.) have no dietary requirements for niacin because of bacterial synthesis in the rumen. 

The enzyme complex that catalyses steps d to/of Fig. 25-20 has an unusual composition. An a3 trimer of 23.5-kDa subunits is contained within an icosahe-dral shell of 60 16-kDa (3 subunits, similar to the protein coats of the icosahedral viruses (Chapter 7). The (3 subunits catalyze the formation of dimethylribityllu-mazine (steps d, e), while the a3 trimer catalyzes the dismutation reaction of step/, the final step in riboflavin formation.365 A separate bifunctional bacterial ATP-dependent synthetase phosphorylates riboflavin and adds the adenylyl group to form FAD.366 Two separate mammalian enzymes are required.367 Synthesis of deazaflavins of methanogens (Fig. 15-22) follows pathways similar to those of riboflavin. However, the phenolic ring of the deazaflavin originates from the shikimate pathway.368... 

The synthesis and characterization of inhibitors for lumazine synthase and riboflavin synthase have been pursued by several research groups over extended periods, and compounds with high in vitro activity have been reported/ °" Unfortunately, none of the known compounds had significant in vivo activity. Most probably, the synthetic compounds, being structural analogues of substrates, products, or intermediates, had insufficient drug-like properties. They may have typically failed to penetrate into the bacterial cells. 

Gelfand MS, Mironov AA, Jomantas J, Kozlov YI, Perumov DA A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes. Trends Genet 1999, 15(11) 439—442. 

---