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

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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

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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
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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
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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
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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
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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
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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
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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
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Tables

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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

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