1887

Chapter 23 : Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818388/9781555810535_Chap23-1.gif /docserver/preview/fulltext/10.1128/9781555818388/9781555810535_Chap23-2.gif

Abstract:

This chapter reviews current knowledge of the bio-synthetic pathways for four vitamins (riboflavin, bio-tin, folic acid, and cobalamin) in . Biosynthesis of these vitamins has been studied in , , and . Riboflavin, also called vitamin B, is unique among the vitamins because more is known about the riboflavin (rib) biosynthetic genes in than is known for any other bacterium. The chapter discusses the organization and regulation of the riboflavin biosynthetic genes and presents results from laboratory on how this information can be used to enhance vitamin production by. The molecular genetics and enzymology of the biosynthesis of biotin, also called vitamin B8 or vitamin H, in bacteria have been studied extensively. Enzymatic steps in the biosynthesis of folic acid in enteric bacteria have been extensively are outlined. The chapter focuses on recently characterized genes known to be involved in folic acid biosynthesis. Vitamin B12, a complex organic molecule, is the largest of all the vitamins. Most current knowledge of genetic pathways involved in vitamin B or cobalamin biosynthesis comes from studies of .

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23

Key Concept Ranking

Transcription Start Site
0.5110872
0.5110872
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Bacterial riboflavin biosynthetic pathway. The corresponding intermediates shown are those produced by and . Structure 1, GTP; structure 2, 2,5-diamino-6-(ribosylamino)-4(3H)-pyrimidinone 5′-phosphate; structure 3, 5-amino-6-(ribosylamino)-2,4(lH,3H)-pyrimidinedione 5′-phosphate; structure 4, 5-amino-6-(ribitylamino)-2,4(lH,3H)-pyrimidinedione 5′-phosphate; structure 5, 5-amino-6-(ribitylamino)-2,4(lH,3H)-pyrimidinedione; structure 6, ribulose 5′-phosphate; structure 7, 3,4-dihydroxy-2-butanone 4-phosphate; structure 8, 6,7-dimethyl-8-ribityllumazine; structure 9, riboflavin. The enzymes that catalyze these reactions in are listed in Table 1 . Structures are adapted from Bacher ( ).

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Structure of the riboflavin operon determined from the nucleotide sequence. Locations of the structural genes (), A promoter regions (), and regulatory site are shown in the upper diagram. Assignment of the genes to the indicated biosynthetic enzymes is described in the text. Tentatively identified genes ORF1 and ORF6 appear not to be involved in riboflavin synthesis. The bottom diagram indicates die rib-specific polycistronic RNA transcripts detected by Northern hybridization. Symbols: , Bacillus ribosome-binding sites (RBS); , start sites of transcription for -recognized promoters P, and P; putative rho-independent transcription termination sites (the located within ribO is postulated to be part of a transcriptional termination-antitermination regulatory mechanism). Not all restriction enzyme sites are shown, aa, amino acids.

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Biotin biosynthesis pathway in Adapted from Gloeckler et al. ( ). SCoA, coenzyme A; Ala, alanine; PLP, pyridoxal 5′-phosphate; SAM, S-adenosylmethionine.

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Schematic diagram of cloned and sequenced parts of the biotin operons of ( ). Putative transcription termination and operator sites are indicated by the symbols and *, respectively ( ).

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Folic acid biosynthesis pathway. Adapted from Brown and Williamson ( ). Where known, the genes encoding the enzymes are indicated.

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

Schematic diagram of cloned and sequenced part of a folic acid operon of ( ).

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7
Figure 7

De novo synthesis of cobalamin. The corresponding intermediates shown are those produced by , which are presumably the same as those produced by . Branch I of the pathway represents synthesis of the corrinoid ring, branch II represents synthesis of DMBI, and branch III represents assembly of the several parts to form the mature cobalamin molecule, cobI, cobII, and cobIII represents mutations that block synthesis within each of these branches, respectively; cobA mutations block formation of adenosylated cobyric acid within the branch I pathway. Encircled compounds are those that make a direct contribution to the final structure. Abbreviations: ALA, 5-aminolevulinic acid; Ado-Cbi, adenosylated cobinamide; Ado-Cby, adenosylated cobyric acid; DMBI, 5,6-dimethylbenzimidazole; DMBI-RP, l-α-D-ribofuranosido-DMBI; FMN, flavin mononucleotide; GDP-Cobinamide, guanosine diphosphocobinamide; Glu, glutamic acid; H2SHC, dihydrosirohydrochlorin; NaMN, nicotinic acid mononucleotide; PBG, porphyrobilinogen; SAM; S-adenosylmethionine; Thr, L-threonine. Adapted from Jeter et al. ( ) and Escalante-Semerena et al. ( ).

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818388.chap23
1. Avissar, Y. J.,, and S. I. Beale. 1989. Identification of the enzymatic basis for δ-aminolevulinic acid auxotrophy in a hemA mutant of Escherichia coli. J. Bacteriol. 171:29192924.
2. Babitzke, P.,, P. Gollnick,, and C. Yanofsky. 1992. The mtrAB operon of Bacillus subtilis encodes GTP cyclohydrolase I (MtrA), an enzyme involved in folic acid biosynthesis, and MtrB, a regulator of tryptophan biosynthesis.J. Bacteriol. 174:20592064.
3. Bacher, A., 1991. Biosynthesis of flavins, p. 215259. In F. Muller (ed.), Chemistry and Biochemistry of Flavins, vol. 1. Chemical Rubber Co., Boca Raton, Fla..
4. Bacher, A.,, R. Baur,, U. Eggers,, H. Harders,, M. K. Otto,, and H. Schnepple. 1980. Riboflavin synthases of Bacillus subtilis: purification and properties. J. Biol. Chem. 255:632637.
5. Bacher, A.,, R. Baur,, U. Eggers,, H. Harders,, and H. Schnepple,. 1976. Riboflavin synthases of Bacillus subtilis, p. 729732. In T. P. Singer (ed.), Flavins and Flavoproteins. Biological and Medical Press, Amsterdam.
6. Bacher, A.,, and R. Ladenstein,. 1991. The lumazine synthase/riboflavin synthase complex of Bacillus subtilis, p. 293316. In F. Muller (ed.), Chemistry and Biochemistry of Flavins, vol. 1. Chemical Rubber Co., Boca Raton, Fla..
7. Bacher, A.,, Q. LeVan,, P. J. Keller,, and H. G. Floss. 1985. Biosynthesis of riboflavin. Incorporation of multiply 13C-labeled precursors into the xylene ring. J. Am. Chem. Soc. 107:63806385.
8. Bacher, A.,, H. C. Ludwig,, H. Schnepple,, and Y. Ben-Shaul. 1986. Heavy riboflavin synthase from Bacillus subtilis. Quaternary structure and reaggregation. J. Mol. Biol. 187:7586.
9. Bacher, A.,, B. Mailander,, R. Baur,, U. Eggers,, H. Harders,, and H. Schnepple,. 1976. Studies on the biosynthesis of riboflavin, p. 285290. In W. Pfleiderer (ed.), Chemistry and Biology of Pteridines. Walter de Gruyter, Berlin.
10. Bacher, A.,, G. Neuberger,, and R. Volk,. 1986. Enzymatic synthesis of 6,7-dimethyI-8-ribityllumazine, p. 227230. In B. A. Cooper, and V. M. Whitehead (ed.), Chemistry and Biology of Pteridines. Walter de Gruyter, Berlin.
11. Bacher, A.,, H. Schnepple,, B. Mailander,, M. K. Otto,, and Y. Ben-Shaul,. 1980. Structure and function of the riboflavin synthase complex of Bacillus subtilis, p. 579586. In K. Yagi, and T. Yamano (ed.), Flavins and Flavoproteins. Japan Scientific Societies Press, Tokyo.
12. Bacher, A.,, R. Volk,, P. J. Keller,, H. G. Floss,, Q. LeVan,, W. Eisenreich,, and B. Schwarzkopf,. 1988. Biosynthesis of flavins and deazaflavins, p. 431440. In D. E. Edmondson, and D. B. McCormick (ed.), Flavins and Flavoproteins. Walter de Gruyter, Berlin.
13. Bachmann, B. J. 1990. Linkage map of Escherichia coli K-12, edition 8. Microbiol. Rev. 54:130197.
14. Bandrln, S. V.,, P. M. Rabinovich,, and A. I. Stepanov. 1983. Three linkage groups of genes involved in riboflavine biosynthesis in Escherichia coli. Sov. Genet. 19: 11031109.
15. Berek, I.,, A. Miczak,, I. Kiss,, G. Ivanovics,, and I. Durko. 1975. Genetic and biochemical analysis of hemin dependent mutants of Bacillus subtilis. Acta Microbiol. Acad. Sci. Hung. 22:157167.
16. Bognar, A. L.,, C. Osborne,, and B. Shane. 1987. Primary structure of the Escherichia coli folC gene and its folylpolyglutamate synthetase-dihydrofolate synthetase product and regulation of expression by an upstream gene. J. Biol. Chem. 262:1233712342.
17. Bognar, A. L.,, C. Osborne,, B. Shane,, S. C. Singer,, and R. Ferone. 1985. Folylpoly-^glutamate synthetase-dihydrofolate synthetase. Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product. J. Biol. Chem. 260:56255630.
18. Bresler, S. E.,, E. I. Cherepenko,, T. P. Chernik,, V. L. Kalinin,, and D. A. Perumov. 1970. Investigation of the operon of riboflavin synthesis in Bacillus subtilis. 1. Genetic mapping of the linkage group. Genetika 6:116124.
19. Bresler, S. E.,, E. I. Cherepenko,, and D. A. Perumov. 1970. Investigation of the operon of riboflavin synthesis in Bacillus subtilis. II. Biochemical study of regulator mutations. Genetika 6:126135.
20. Bresler, S. E.,, I. E. Cherepenko,, and D. A. Perumov. 1971. Investigation of the operon of riboflavin biosynthesis in Bacillus subtilis. III. Production and properties of mutants with a complex regulatory genotype. Genetika 7:117123.
21. Bresler, S. E.,, E. A. Glazunov,, and D. A. Perumov. 1972. Study of the operon of riboflavin biosynthesis in Bacillus subtilis. IV. Regulation of the synthesis of riboflavin synthetase. Investigation of riboflavin transport through the cell membrane. Genetika 8:109118.
22. Bresler, S. E.,, E. A. Glazunov,, D. A. Perumov,, and T. P. Chernik. 1977. Investigation of the operon of riboflavin biosynthesis in Bacillus subtilis. XIII. Genetic and biochemical investigation of mutants related to intermediate stages of biosynthesis. Genetika 13:20072016.
23. Bresler, S. E.,, G. F. Gorinchuk,, T. P. Chernik,, and D. A. Perumov. 1978. Riboflavin operon in Bacillus subtilis. XV. Investigation of the mutants relating to initial steps of biosynthesis. The origin of ribityl side chain. Genetika 14:20822090.
24. Bresler, S. E.,, and D. A. Perumov. 1979. Riboflavin operon in Bacillus subtilis. Regulation of GTP-cyclohydrolase synthesis in strains of different genotypes. Genetika 15:967971.
25. Bresler, S. E.,, D. A. Perumov,, T. P. Chernik,, and E. A. Glazunov. 1976. Investigation of the operon of riboflavin bisynthesis in Bacillus subtilis. X. Genetic and biochemical study of mutants that accumulate 6-methyl-7-(1',2'-dihydroxyethyl)-8-ribityllumazine. Genetika 12:8391.
26. Bresler, S. E.,, D. A. Perumov,, E. A. Glazunov,, T. N. Shevchenko,, and T. P. Chernik. 1977. Investigation of the operon of riboflavin biosynthesis in Bacillus subtilis. XII. Determination of the ATP: riboflavin-5'-phosphotransferase and riboflavin synthetase content in cells with different genotypes. Genetika 13:880887.
27. Bresler, S. E.,, D. A. Perumov,, A. P. Skvortsova,, T. P. Chernik,, and T. N. Shevchenko. 1975. Study of the riboflavin operon of Bacillus subtilis. VIII. Genetic mapping of ribC markers in relation to the cluster of structural genes. Genetika 11:95100.
28. Brey, R. N.,, C. D. B. Banner,, and J. B. Wolf. 1986. Cloning of multiple genes involved with cobalamin (vitamin B12) biosynthesis in Bacillus megaterium. J. Bacteriol. 167:623630.
29. Brown, G. M.,, and H. Williamson. 1982. Biosynthesis of riboflavin, folic acid, thiamine, and pantothenic acid. Adv. Enzymol. Relat. Areas Mol. Biol. 53:345381.
30. Brown, G. M.,, and J. M. Williamson,. 1987. Biosynthesis of folic acid, riboflavin, thiamine, and pantothenic acid, p. 521538. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C..
31. Brown, G. M.,, J. Yim,, Y. Suzuki,, M. C. Heine,, and F. Foor,. 1975. The enzymatic synthesis of pterins in Escherichia coli, p. 219245. In W. Pfleiderer (ed.), Chemistry and Biology of Pteridines. Walter de Gruyter, Berlin.
32. Burrows, R. B.,, and G. M. Brown. 1978. Presence in Escherichia coli of a deaminase and a reductase involved in biosynthesis of riboflavin. J. Bacteriol. 136: 657667.
33. Chen, N.-Y.,, F.-M. Hu,, and H. Paulus. 1987. Nucleotide sequence of the overlapping genes for the subunits of Bacillus subtilis aspartokinase II and their control regions. J. Biol. Chem. 262:87878798.
34. Chernlk, T. P.,, S. E. Bresler,, V. V. Machkovsky,, and D. A. Perumov. 1979. Riboflavin-biosynthesis operon in Bacillus subtilis. XVI. Localization of group ribC markers on the chromosome. Genetika 15:15691577.
35. Chernlk, T. P. A.,, P. Skvortsova,, T. N. Shevchenko,, D. A. Perumov,, and S. E. Bresler. 1974. Riboflavin operon in Bacillus subtilis. VI. Nature and properties of mutants constitutive in the presence of flavin mononucleotide. Genetika 10:94104.
36. Chikindas, M. L.,, E. V. Luk'yanov,, P. M. Rabinovlch,, and A. I. Stepanov. 1986. Study of the 210° region of the Bacillus subtilis chromosome. Mol. Genet. Mikrobiol. Virusol. 2:2024.
37. Chikindas, M. L.,( V. N. Mlronov,, E. V. Luk'yanov,, Y. R. Boretskii,, L. S. Artyunova,, P. M. Rabinovlch,, and A. I. Stepanov. 1987. Determination of the bounds of the Bacillus subtilis riboflavin operon. Mol. Genet. Mikrobiol. Virusol. 4:2226.
38. Chikindas, M. L.,, G. I. Morozov,, V. N. Mlronov,, E. V. Luk'yanov,, V. V. Emel'yanov,, and A. I. Stepanov. 1988. Regulatory regions of the operon for biosynthesis of Bacillus subtilis riboflavin. Dokl. Akad. Nauk SSSR 298: 9971000.
39. Cronan, J. E., Jr. 1989. The E. coli bio operon: transcriptional repression by an essential protein modification enzyme. Cell 58:427429.
40. Debarboullle, M.,, M. Arnaud,, A. Fouet,, A. Kller,, and G. Rapoport. 1990. The sacT gene regulating the sacPA operon in Bacillus subtilis shares strong homology with transcriptional antiterminators. J. Bacteriol. 172:39663973.
41. Ebbole, D. J.,, and H. Zalkin. 1987. Cloning and characterization of a 12-gene cluster from Bacillus subtilis encoding nine enzymes for de novo purine nucleotide synthesis. J. Biol. Chem. 262:82748287.
42. Ebbole, D. J.,, and H. Zalkin. 1988. Detection of pur operon-attenuated mRNA and accumulated degradation intermediates in Bacillus subtilis. J. Biol. Chem. 263:1089410902.
43. Ebbole, D. J.,, and H. Zalkin. 1989. Interaction of a putative repressor protein with an extended control region of the Bacillus subtilis pur operon. J. Biol. Chem. 264:35533561.
44. Eisenberg, M. A. 1984. Regulation of the biotin operon. Ann. N.Y. Acad. Sci. 447:335349.
45. Eisenberg, M. A., 1987. Biosynthesis of biotin and lipoic acid, p. 544550. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium : Cellular and Molecular Biology, vol 1. American Society for Microbiology, Washington, D.C..
46. Elliott, T. 1989. Cloning, genetic characterization, and nucleotide sequence of the hemA-prfA operon of Salmonella typhimurium. J. Bacteriol. 171:39483960.
47. Enei, H.,, K. Sato,, Y. Anzai,, and H. Okada. August 1975. Fermentative production of riboflavine. U.S. patent 3,900,368.
48. Escalante-Semerena, J. C.,, and J. R. Roth. 1987. Regulation of cobalamin biosynthetic operons in Salmonella typhimurium. J. Bacteriol. 169:22512258.
49. Escalante-Semerena, J. C.,, S.-J. Suh,, and J. R. Roth. 1990. cobA function is required for both de novo cobalamin biosynthesis and assimilation of exogenous corrinoids in Salmonella typhimurium. J. Bacteriol. 172:273280.
50. Floss, G. H.,, Q. LeVan,, P. J. Keller,, and A. Bacher. 1983. Biosynthesis of riboflavin. An unusual rearrangement in the formation of 6,7-dimenthyl-8-ribiryllumazine. J. Am. Chem. Soc. 105:24932495.
51. Foor, F.,, and G. M. Brown. 1975. Purification and properties of guanosine triphosphate cyclohydrolase II from Escherichia coli. J. Biol. Chem. 250:35453551.
52. Glazunov, E. A.,, S. E. Bresler,, and D. A. Perumov. 1974. Investigation of the riboflavin operon of Bacillus subtilis. VII. Biochemical study of mutants relating to early stages of biosynthesis. Genetika 10:8392.
53. Gloeckler, R.,, I. Ohsawa,, D. Speck,, C. Ledoux,, S. Bernard,, M. Zinsius,, D. Villeval,, T. Kisou,, K. Ka-mogawa,, and Y. Lemolne. 1990. Cloning and characterization of the Bacillus sphaericus genes controlling the bioconversion of pimelate into dethiobiotin. Gene 87: 6370.
54. Gollnick, P.,, S. Ishino,, M. I. Kuroda,, D. J. Henner,, and C. Yanofsky. 1990. The mtr locus is a two-gene operon required for transcription attenuation in the trp operon of Bacillus subtilis. Genetics 87:87268730.
55. Goodwin, T. W.,, and A. A. Horton. 1961. Biosynthesis of riboflavin in cell-free systems. Nature (London) 191: 772774.
56. Green, J. M.,, and B. P. Nichols. 1991. p-Aminobenzoate biosynthesis in Escherichia coli. J. Biol. Chem. 266: 1297112975.
57. Hanson, M.,, L. Rutberg,, I. Schröder,, and L. Hederstedt. 1991. The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes for the biosynthetic pathway from glutamate to uroporphyrinogen III. J. Bacteriol. 173:25902599.
58. Harzer, G.,, H. Rokos,, M. K. Otto,, A. Bacher,, and S. Ghisla. 1978. Biosynthesis of riboflavin. 6,7-Dimethyl-8-ribityllumazine 5'-phosphate is not a substrate for riboflavin synthase. Biochim. Biophys. Acta 540:4854.
59. Henner, D. J.,, L. Band,, and H. Shlmotsu. 1984. Nucleotide sequence of the Bacillus subtilis tryptophan operon. Gene 34:169177.
60. Henner, D. J.,, and J. A. Hoch,. 1982. The genetic map of Bacillus subtilis, p. 133. In D. Dubnau (ed.), The Molecular Biology of the Bacilli. Academic Press, Inc., New York.
61. Howard, P. K.,, J. Shaw,, and A. J. Otsuka. 1985. Nucleotide sequence of the birk gene encoding the biotin operon repressor and biotin holoenzyme synthetase functions of Escherichia coli. Gene 35:321331.
62. Iwahara, S.,, M. Klkuchl,, T. Tochikura,, and K. Ogata. 1966. Some properties of avidin-uncombinable unknown biotin-vitamer produced by Bacillus sp. and its role in biosynthesis of desthiobiotin. Agric. Biol. Chem. 30:304306.
63. Izumi, Y.,, Y. Kano,, K. Inagaski,, N. Kawase,, Y. Tani,, and H. Yamada. 1981. Characterization of biotin biosynthetic enzymes of Bacillus sphaericus: a desthiobiotin producing bacterium. Agric. Biol. Chem. 45:19831989.
64. Izumi, Y.,, H. Morita,, Y. Tani,, and K. Ogata. 1974. The pimelyl-CoA synthetase responsible for the first step in biotin biosynthesis by microorganisms. Agric. Biol. Chem. 38:22572262.
65. Izumi, Y.,, H. Morita,, K. Sato,, Y. Tani,, and K. Ogata. 1972. Synthesis of biotin-vitamers from pimelic acid and coenzyme A by cell-free extracts of various bacteria. Biochim. Biophys. Acta 264:210213.
66. Izumi, Y.,, H. Morita,, Y. Tani,, and K. Ogata. 1973. Partial purification and some properties of 7-keto-8-aminopelargonic acid synthetase, an enzyme involved in biotin biosynthesis. Agric. Biol. Chem. 37:13271333.
67. Izumi, Y.,, and K. Ogata. 1975. Some aspects of the microbial production of biotin. Adv. Appl. Microbiol. 22:145176.
68. Izumi, Y.,, K. Sato,, Y. Tani,, and K. Ogata. 1973. Distribution of 7-keto-8-aminopelargonic acid synthetase in bacteria and the control mechanism of the enzyme activity. Agric. Biol. Chem. 37:13351340.
69. Jeter, R.,, J. C. Escalante-Semerena,, D. Roof,, B. Ollvera,, and J. Roth,. 1987. Synthesis and use of vitamin B12, p. 551556. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimwrium: Cellular and Molecular Biology, vol. 1. American Society for Microbiology, Washington, D.C.
70. Jeter, R. M.,, B. M. Olivera,, and J. R. Roth. 1984. Salmonella typhimwrium synthesizes cobalamin (vitamin Bj2) de novo under anaerobic growth conditions. J. Bacteriol. 159:206213.
71. Kane, J. F. 1977. Regulation of a common amidotrans-ferase subunit. J. Bacteriol. 132:419425.
72. Kane, J. F.,, W. M. Holmes,, and R. A. Jensen. 1972. Metabolic interlock: the dual function of a folate pathway gene as an extraoperonic gene of tryptophan biosynthesis.J. Biol. Chem. 247:15871596.
73. Katzenmeier, G.,, C. Schmld,, J. Kellermann,, F. Lottspelch,, and A. Bacher. 1991. Sequence of GTP cyclohydrolase I from Escherichia coli. Biol. Chem. Hoppe-Seyler 372:991997.
74. Kiss, I.,, I. Berek,, and G. Ivanovics. 1971. Mapping the δ-aminolevulinic acid synthetase locus in Bacillus subtilis. J. Gen. Microbiol. 66:153159.
75. Konishi, S.,, and T. Shiro. 1968. Fermentation production of guanosine by 8-azaguanine resistance of Bacillus subtilis. Agric. Biol. Chem. 32:396398.
76. Kreneva, R. A., and D. A. Perumov. 1990. Genetic mapping of regulatory mutations of Bacillus subtilis riboflavin operon. Mol. Gen. Genet. 222:467469.
77.Kukanova, A. Y., V. G. Zhdanov, and A. I. Stepanov. 1982. The roseoflavin-resistant mutants of Bacillus subtilis. Genetika 18:319321.
78. Ladenstein, R.,, B. Meyer,, R. Huber,, H. Labischinski,, K. Bartels,, H. D. Bartunik,, L. Bachmann,, H. C. Ludwlg,, and A. Bacher. 1986. Heavy riboflavin synthase from Bacillus subtilis. Particle dimensions, crystal packing and molecular symmetry. J. Mol. Biol. 187:87100.
79. Le Van, Q.,, P. J. Keller,, D. H. Brown,, H. G. Floss,, and A. Bacher. 1985. Biosynthesis of riboflavin in Bacillus subtilis: origin of the four-carbon moiety. J. Bacteriol. 162:12801284.
80. Lee, G.,, and J. Pero. 1981. Conserved nucleotide sequences in temporally-controlled phage promoters. J. Mol. Biol. 152:247265.
81. Logvinenko, E. M.,, G. M. Shavlovsky,, and N. Y. Tsarenko. 1984. The role of iron in regulation of 6,7-dimethyl-8-ribitylIumazine synthetase synthesis in flavinogenic yeasts. Biokhimiya 49:4550.
82. Logvinenko, E. M.,, G. M. Shavlovsky,, A. E. Zakal'sky,, and I. V. Zakhodylo. 1982. Biosynthesis of 6,7-dimeth-yl-8-ribityllumazine in yeast extracts of Pichia guilliermondii. Biokhimiya 47:931936.
83. Lopez, P.,, M. Espinosa,, B. Greenberg,, and S. A. Lacks. 1987. Sulfonamide resistance in Streptococcus pneumoniae: DNA sequence of the gene encoding dihydropteroate synthase and characterization of the enzyme. J. Bacteriol. 169:43204326.
84. Lopez, P.,, B. Greenberg,, and S. A. Lacks. 1990. DNA sequence of folate biosynthesis gene sulD, encoding hydroxymethyldihydropterin pyrophosphokinase in Streptococcus pneumoniae, and characterization of the enzyme. J. Bacteriol. 172:47664774.
85. Ludwig, H. C.,, F. Lottspeich,, A. Henschen,, R. Ladenstein,, and A. Bacher. 1987. Heavy riboflavin synthase of Bacillus subtilis: primary structure of the β subunit. J. Biol. Chem. 262:10161021.
86. Lundrlgan, M. D.,, L. C. DeVeaux,, B. J. Mann,, and R. J. Kadner. 1987. Separate regulatory systems for repression of metE and btuB by vitamin B12 in Escherichia coli. Mol. Gen. Genet. 206:401407.
87. Maley, G. F.,, D. U. Guarino,, and F. Maley. 1983. Complete amino acid sequence of an allosteric enzyme, T2 bacteriophage deoxycytidylate deaminase. J. Biol. Chem. 258:82908297.
88. Margolis, P. S.,, A. Drlks,, and R. Losick. 1993. Sporulation gene spoIIB from Bacillus subtilis. J. Bacteriol. 175:528540.
89. Matsui, H.,, K. Sato,, H. Enei,, and Y. Hirose. 1977. Mutation of an inosine-producing strain of Bacillus subtilis to DL-methionine sulfoxide resistance for guanosine production. Appl. Environ. Microbiol. 34: 337341.
90. Matsui, H.,, K. Sato,, H. Enei,, and Y. Hirose. 1979. A guanosine-producing mutant of Bacillus subtilis with high productivity. Agric. Biol. Chem. 43:393394.
91. Matsui, H.,, K. Sato,, H. Enei,, and Y. Hirose. 1979. Production of guanosine by psicofuranine and decoyinine resistant mutants of Bacillus subtilis. Agric. Biol. Chem. 43:17391744.
92. Matsui, K.,, H.-C. Wang,, T. Hirota,, H. Matsukawa,, S. Kasai,, K. Shinagawa,, and S. Otani. 1982. Riboflavin production by roseoflavin-resistant strains of some bacteria. Agric. Biol. Chem. 46:20032008.
93. McDonald, K. O.,, and J. W. F. Burke. 1982. Cloning of the Bacillus subtilis sulfanilamide resistance gene in Bacillus subtilis. J. Bacteriol. 149:391394.
94. Miczak, A.,, B. Progai,, and I. Berek. 1979. Mapping the uroporphyrinogen III cosynthase locus in Bacillus subtilis. Mol. Gen. Genet. 174:293295.
95. Mironov, V. N.,, M. L. Chikindas,, A. S. Kraev,, A. I. Stepanov,, and K. G. Skryabin. 1990. Operon organization of genes of riboflavin biosynthesis in Bacillus subtilis. Dok. Akad. Nauk SSSR 312:237240.
96. Mironov, V. N.,, A. S. Kraev,, B. K. Chernov,, A. V. Ul'yanov,, Y. B. Golva,, G. E. Pozmogova,, M. L. Simonova,, V. K. Gordeev,, A. I. Stepanov,, and K. G. Skryabin. 1989. Genes of riboflavin biosynthesis of Bacillus subtilis—complete primary structure and model of organization. Dokl. Adad. Nauk SSSR 305:482486.
97. Mironov, V. N.,, D. A. Perumov,, A. S. Kraev,, A. I. Stepanov,, and K. G. Skryabln. 1990. Unusual structure in the regulation region of the Bacillus subtilis riboflavin biosynthesis operon. Mol. Biol. (Moscow) 24:256261.
98. Mohan, S.,, J. Aghion,, N. Guillen,, and D. Dubnau. 1989. Molecular cloning and characterization of comC, a late competence gene of Bacillus subtilis. J. Bacteriol. 171: 60436051.
99. Morozov, G. I.,, P. M. Rabinovich,, S. V. Bandrin,, and A. I. Stepanov. 1984. Organization of Bacillus subtilis riboflavin operon. Mol. Genet. Mikrobiol. Virusol. 7:4246.
100. Morozov, G. I.,, P. M. Rabinovich,, V. V. Emel'yanov,, and A. I. Stepanov. 1985. Operon for biosynthesis of Bacillus subtilis riboflavin contains additional promoters. Mol. Genet. Mikrobiol. Virusol. 12:1419.
101. Morozov, G. I.,, P. M. Rabinovich,, and A. I. Stepanov. 1984. Operator position in the coupling group of structural genes of the Bacillus subtilis riboflavin operon. Mol. Genet. Mikrobiol. Virusol. 11:1116.
102. Neuberger, G.,, and A. Bacher. 1986. Biosynthesis of riboflavin. Enzymatic formation of 6,7-dimethyl-8-ribityllumazine by heavy riboflavin synthase from Bacillus subtilis. Biochem. Biophys. Res. Commun. 139:11111116.
103. Nichols, B. P.,, A. M. Seibold,, and S. Z. Boktor. 1989. para-Aminobenzoate synthesis from chorismate occurs in two steps. J. Biol. Chem. 264:85878601.
104. Nielsen, P.,, G. Neuberger,, I. Fujii,, D. H. Brown,, P. J. Keller,, H. G. Floss,, and A. Bacher. 1986. Biosynthesis of riboflavin. Enzymatic formation of 6,7-dimethyl-8-ribityllumazine from pentose phosphates. J. Biol. Chem. 261:36613669.
105. Ohsawa, I.,, D. Speck,, T. Kisou,, K. Hayakawa,, M. Zinsius,, R. Gloeckler,, Y. Lemoine,, and K. Kamogawa. 1989. Cloning of the biotin synthetase gene from Bacilhis sphaericus and expression in Escherichia coli and Bacilli. Gene 80:3948.
106. O'Neill, G. P.,, M.-W. Chen,, and D. S611. 1989. δ-Aminolevulinic acid biosynthesis in Escherichia coli and Bacillus subtilis involves formation of glutamyl-tRNA. FEMS Microbiol. Lett. 60:255260.
107. O'Regan, M.,, R. Gloeckler,, S. Bernard,, C. Ledoux,, I. Ohsawa,, and Y. Lemoine. 1989. Nucleotide sequence of the bioH gene of Escherichia coli. Nucleic Acids Res. 17:8004.
108. Otsuka, A. J.,, M. R. Buoncristianl,, P. K. Howard,, J. Flanun,, C. Johnson,, R. Yamamoto,, K. Uchlda,, C. Cook,, J. Ruppert,, and J. Matsuzakl. 1988. The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J. Biol. Chem. 263:1957719585.
109. Pal, C. H. 1975. Genetics of biotin biosynthesis in Bacillus subtilis. J. Bacteriol. 121:18.
110. Perkins, J. B.,, J. G. Pero,, and A. Sloma. January 1991. Riboflavin overproducing strains of bacteria. European patent application 0405370.
111. Perkins, J. B.,, A. Sloma,, and J. Pero. Unpublished data.
112. Perumov, D. A.,, E. A. Glazunov,, and G. F. Gorlnchuk. 1985. Riboflavin operon in Bacillus subtilis. XVII. Regulatory functions of intermediate products and their derivatives. Genetika 22:748754.
113. Petricek, M.,, L. Rutberg,, I. Schroder,, and L. Hederstedt. 1990. Cloning and characterization of the hemA region of the Bacillus subtilis chromosome. J. Bacteriol. 172:22502258.
114. Ploux, O.,, and A. Marquet. 1992. The 8-amino-7-oxoate pelargon synthase from Bacillus sphaericus. Purification and preliminary characterization of the cloned enzyme overproduced in Escherichia coli. Biochem. J. 283:327331.
115. Ploux, O.,, P. Soularue,, A. Marquet,, R. Gloeckler,, and Y. Lemoine. 1992. Investigation of the first step of biotin biosynthesis in Bacillus sphaericus. Purification and characterization of the pimeloyl-CoA synthase, and uptake of pimelate. Biochem. J. 287:685690.
116. Quinn, C. L.,, B. T. Stephenson,, and R. L. Switzer. 1991. Functional organization and nucleotide sequence of the Bacillus subtilis pyrimidine biosynthetic operon. J. Biol. Chem. 266:91139127.
117. Rabinovlch, P. M.,, M. Y. Beburov,, Z. K. Llnevlch,, and A. I. Stepanov. 1978. Amplification of Bacillus subtilis riboflavin operon in Escherichia coli. Genetika 14:16961705.
117a.. Richter, G.,, H. Ritz,, G. Katzenmeier,, R. Volk,, A. Kohnle,, F. Lottspeich,, D. Allendorf,, and A. Bacher. Biosynthesis of riboflavin. Cloning, sequencing, mapping and expression of the gene coding for GTPcyclohydrolase II of Escherichia coli. Submitted for publication.
118. Richter, G.,, R. Volk,, C. Krieger,, H.-W. Lahm,, U. Rothltsberger,, and A. Bacher. 1992. Biosynthesis of riboflavin: cloning, sequencing, and expression of the gene coding 3,4-dihydroxy-2-butanone 4-phosphate synthase of Escherichia coli. J. Bacteriol. 174:40504056.
118a.. Robin, C.,, F. Blance,, L. Cauchois,, B. Cameron,, M. Couder,, and J. Crouzet. 1991. Primary structure, expression in Escherichia coli, and properties of S-adenosyl-L-methionine: uroporphyrinogen III methyl-transferase from Bacillus megaterium. J. Bacteriol. 173:48931896.
119. Rolfe, B.,, and M. A. Eisenberg. 1968. Genetic and biochemical analysis of the biotin loci of Escherichia coli K-12. J. Bacteriol. 96:515524.
120. Saxlld, H. H.,, and P. Nygaard. 1987. Genetic and physiological characterization of Bacillus subtilis mutants resistant to purine analogs. J. Bacteriol. 169:29772983.
121. Schott, K.,, J. Kellermann,, F. Lottspeich,, and A. Bacher. 1990. Riboflavin synthases of Bacillus subtilis: purification and amino acid sequence of the α subunit. J. Biol. Chem. 265:42044209.
122. Shane, B. 1980. Pteroylpoly (γ-glutamate) synthesis by Corynebacterium species. Purification and properties of folylpoly(y-glutamate) synthetase. J. Biol. Chem. 255: 56555662.
123. Shavlovsky, G. M.,, G. E. Teslyar,, and L. P. Strugovshchlkova. 1982. Regulation of flavinogenesis in riboflavin-dependent Escherichia coli mutants. Mikrobiologiya 51:986992.
124. Shimotsu, H.,, M. Kuroda,, C. Yanofsky,, and D. J. Henner. 1986. Novel form of transcription attenuation regulates expression of the Bacillus subtilis tryptophan operon. J. Bacteriol. 166:461471.
125. Slock, J.,, D. P. Stahly,, C.-Y. Han,, E. W. Six,, and I. P. Crawford. 1990. An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid, and the dihydropteroate synthase gene. J. Bacteriol. 172:72117226.
126. Song, B.-H.,, and J. Neuhard. 1989. Chromosomal location, cloning and nucleotide sequence of the Bacillus subtilis cdd gene encoding cytidine/deoxycytidine deaminase. Mol. Gen. Genet. 216:462468.
127. Speck, D.,, I. Ohsawa,, R. Gloeckler,, M. Zinsius,, S. Bernard,, C. Ledoux,, T. Klsou,, K. Kamogawa,, and Y. Lemoine. 1991. Isolation of Bacillus sphaericus mutants affected in their control of biotin synthesis: evidence for transcriptional regulation of the bio genes. Gene 108: 3945.
128. Stepanov, A. L.,, A. Y. Kukanova,, E. A. Glazunov,, and V. G. Zhdanov. 1977. Analogs of riboflavin and lumiflavin and derivatives of alloxazine. II. Effect of roseoflavin on synthesis of 6,7-dimethyl-8-ribityllumazine and riboflavin synthetase and growth of Bacillus subtilis. Genetika 13:490495.
129. Stepanov, A. I.,, V. G. Zhdanov,, A. Y. Kukanova,, M. Y. Khaikinson,, P. M. Rabinovlch,, J. A. V. Iomantas,, and Z. M. Galushklna. December 1984. Method for preparing riboflavin. French patent application 3599355.
129a.. Taura, T.,, C. Ueguchi,, K. Shiba,, and K. Ito. 1992. Insertional disruption of the nusB (ssyB) gene leads to cold-sensitive growth of Escherichia coli and suppression of the secY24 mutation. Mol. Gen. Genet. 234:429432.
130. Teslyar, G. E.,, and G. M. Shavlovsky. 1983. Localization of the genes coding cyclohexrolase [cyclohydrolase] II and riboflavin synthase on the Escherichia coli K-12 chromosome. Cytol. Genet. 17:5759.
131. Volk, R.,, and A. Bacher. 1988. Biosynthesis of riboflavin. The structure of the four-carbon precursor. J. Am. Chem.Soc. 110:36513653.
132. Wolf, J. B.,, and R. N. Brey. 1986. Isolation and genetic characterizations of Bacillus megaterium cobalamin biosynthesis-deficient mutants. J. Bacteriol. 166:5158.
133. Yamada, H.,, M. Osakai,, Y. Tani,, and Y. Izumi. 1983. Biotin overproduction by biotin analog-resistant mutants of Bacillus sphaericus. Agric. Biol. Chem. 47:10111016.
134. Zalkin, H.,, and D. J. Ebbole. 1988. Organization and regulation of genes encoding biosynthetic enzymes in Bacillus subtilis. J. Biol. Chem. 26:15951598.

Tables

Generic image for table
Table 1

Enzymes, genes, and regulatory elements of riboflavin synthesis in

Citation: Perkins J, Pero J. 1993. Biosynthesis of Riboflavin, Biotin, Folic Acid, and Cobalamin, p 319-334. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch23

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error