If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Flavin Biosynthesis|
Expected Taxonomic Range: Fungi
riboflavin is the precursor for the essential flavin cofactors FMN and FAD, which are used in a wide variety of redox reactions. Riboflavin is also known as vitamin B2, because it is an essential nutrient and can not be synthesized by mammals.
The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of D-ribulose 5-phosphate as substrates. The imidazole ring of GTP is hydrolytically opened, yielding a 4, 5-diaminopyrimidine which is converted to 5-amino-6-(D-ribitylamino)uracil by a sequence of deamination, side chain reduction and dephosphorylation. Condensation of 5-amino-6-(D-ribitylamino)uracil with 1-deoxy-L-glycero-tetrulose 4-phosphate obtained from D-ribulose 5-phosphate results in the formation of 6,7-dimethyl-8-(1-D-ribityl)lumazine. Dismutation of the lumazine derivative yields riboflavin and 5-amino-6-(D-ribitylamino)uracil, which is recycled in the pathway [Bacher00].
The fungal riboflavin biosynthesis pathway and its enzymes are well understood, with the exception of the enzyme catalyzing the dephosphorylation of 5-amino-6-(5-phospho-D-ribitylamino)uracil. This enzyme has not been isolated, and it has been suggested that the reaction may be catalyzed by a phosphatase of broad substrate specificity.
Unlike the bacterial enzymes, many of which are bifunctional and catalyze more than one reaction in the pathway, all of the yeast enzymes are monofunctional, each catalyzing a single pathway reaction.
Different variations of the pathway are found in the different kingdoms of life. A main difference between the fungal and bacterial/plant pathways (see flavin biosynthesis I (bacteria and plants)) is in the order in which two of the enzymes act. Two enzymatic steps are required to convert 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one to 5-amino-6-(5-phospho-D-ribitylamino)uracil - a demaination and a reduction. In bacteria and plants, the deaminase acts first, followed by the reductase (although both steps are catalyzed by a single bifunctional enzyme in some organisms), while in fungi the reductase acts first, followed by the deaminase.
The archaeal pathway also differs in several steps (see flavin biosynthesis II (archaea)).
Bacher97: Bacher A, Richter G, Ritz H, Eberhardt S, Fischer M, Krieger C (1997). "Biosynthesis of riboflavin: GTP cyclohydrolase II, deaminase, and reductase." Methods Enzymol 280;382-9. PMID: 9211333
Baur93: Baur A, Schaaff-Gerstenschlager I, Boles E, Miosga T, Rose M, Zimmermann FK (1993). "Sequence of a 4.8 kb fragment of Saccharomyces cerevisiae chromosome II including three essential open reading frames." Yeast 9(3);289-93. PMID: 8488729
Buitrago93: Buitrago MJ, Gonzalez GA, Saiz JE, Revuelta JL (1993). "Mapping of the RIB1 and RIB7 genes involved in the biosynthesis of riboflavin in Saccharomyces cerevisiae." Yeast 9(10);1099-102. PMID: 8256517
Chatwell06: Chatwell L, Krojer T, Fidler A, Romisch W, Eisenreich W, Bacher A, Huber R, Fischer M (2006). "Biosynthesis of riboflavin: structure and properties of 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate reductase of Methanocaldococcus jannaschii." J Mol Biol 359(5);1334-51. PMID: 16730025
Chi09: Chi A, Rhee S (2009). "The functional annotation of Arabidopsis protein sequences was performed by BLAST queries against a reference set of experimentally verified enzymes. For each Arabidopsis sequence, the enzymatic activity of the top BLAST hit (or hits if they had equivalent E-values) was assigned to the protein if its E-value fell below a specific E-value threshold established for the corresponding enzymatic activity. Note: The annotation thresholds were established by doing a self BLAST of the reference enzyme dataset. For each enzymatic activity represented by multiple proteins, the mean E-value of all the correct hits generated by the self BLAST was selected as the cut-off. All of these means were averaged and used as the cut-off for assigning annotations for any enzymatic activities that were represented by a single protein in the reference dataset."
Eberhardt96: Eberhardt S, Richter G, Gimbel W, Werner T, Bacher A (1996). "Cloning, sequencing, mapping and hyperexpression of the ribC gene coding for riboflavin synthase of Escherichia coli." Eur J Biochem 242(3);712-9. PMID: 9022701
Fischer02: Fischer M, Romisch W, Schiffmann S, Kelly M, Oschkinat H, Steinbacher S, Huber R, Eisenreich W, Richter G, Bacher A (2002). "Biosynthesis of riboflavin in archaea studies on the mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase of Methanococcus jannaschii." J Biol Chem 277(44);41410-6. PMID: 12200440
Fischer04: Fischer M, Schott AK, Romisch W, Ramsperger A, Augustin M, Fidler A, Bacher A, Richter G, Huber R, Eisenreich W (2004). "Evolution of vitamin B2 biosynthesis. A novel class of riboflavin synthase in Archaea." J Mol Biol 343(1);267-78. PMID: 15381435
Fischer05: Fischer M, Haase I, Feicht R, Schramek N, Kohler P, Schieberle P, Bacher A (2005). "Evolution of vitamin B2 biosynthesis: riboflavin synthase of Arabidopsis thaliana and its inhibition by riboflavin." Biol Chem 386(5);417-28. PMID: 15927885
GarciaRamirez95: Garcia-Ramirez JJ, Santos MA, Revuelta JL (1995). "The Saccharomyces cerevisiae RIB4 gene codes for 6,7-dimethyl-8-ribityllumazine synthase involved in riboflavin biosynthesis. Molecular characterization of the gene and purification of the encoded protein." J Biol Chem 270(40);23801-7. PMID: 7559556
Graupner02a: Graupner M, Xu H, White RH (2002). "The pyrimidine nucleotide reductase step in riboflavin and F(420) biosynthesis in archaea proceeds by the eukaryotic route to riboflavin." J Bacteriol 184(7);1952-7. PMID: 11889103
Haase03: Haase I, Mortl S, Kohler P, Bacher A, Fischer M (2003). "Biosynthesis of riboflavin in archaea. 6,7-dimethyl-8-ribityllumazine synthase of Methanococcus jannaschii." Eur J Biochem 270(5);1025-32. PMID: 12603336
Haase13: Haase I, Sarge S, Illarionov B, Laudert D, Hohmann HP, Bacher A, Fischer M (2013). "Enzymes from the haloacid dehalogenase (HAD) superfamily catalyse the elusive dephosphorylation step of riboflavin biosynthesis." Chembiochem 14(17);2272-5. PMID: 24123841
Herz00a: Herz S, Eberhardt S, Bacher A (2000). "Biosynthesis of riboflavin in plants. The ribA gene of Arabidopsis thaliana specifies a bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase." Phytochemistry 53(7);723-31. PMID: 10783978
Hu07: Hu Y, Rolfs A, Bhullar B, Murthy TV, Zhu C, Berger MF, Camargo AA, Kelley F, McCarron S, Jepson D, Richardson A, Raphael J, Moreira D, Taycher E, Zuo D, Mohr S, Kane MF, Williamson J, Simpson A, Bulyk ML, Harlow E, Marsischky G, Kolodner RD, LaBaer J (2007). "Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Genome Res 17(4);536-43. PMID: 17322287
Illarionov01: Illarionov B, Kemter K, Eberhardt S, Richter G, Cushman M, Bacher A (2001). "Riboflavin synthase of Escherichia coli. Effect of single amino acid substitutions on reaction rate and ligand binding properties." J Biol Chem 276(15);11524-30. PMID: 11278450
Showing only 20 references. To show more, press the button "Show all references".
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493