Biosynthesis of Vitamin B<sub>2</sub> (Riboflavin)

Bacher, Adelbert; Eberhardt, Sabine; Fischer, Markus; Kis, Klaus; Richter, Gerald

doi:10.1146/annurev.nutr.20.1.153

Cited by 261 publications

(196 citation statements)

References 86 publications

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“…The genes obtained from the three strains were sequenced and compared with the previously reported sequence of RIB3. 2 The sequences of the D273-10B/A21 and W303-1A genes were identical to the sequence number reported in GenBank™. The rib3 gene isolated TABLE II Respiratory activities of mitochondria Mitochondria were isolated from the parental wild type strain D273-10B/A21 and from the rib3 mutant E280 grown in YPGal and in YPGal supplemented with 25 g/ml riboflavin.…”

Section: Fig 1 Phenotype Of E280supporting

confidence: 62%

“…This region of the insert contains RIB3, a gene of chromosome IV, previously shown to code for DHBP synthase (3). This enzyme catalyzes the conversion of ribose-5-phosphate to 3,4-dihydroxy-2-butanone-4-phosphate, an early precursors in riboflavin synthesis (2). The failure of pG164/ ST31 and pG164/ST32, each containing different halves of RIB3, to restore respiration confirmed the correct identification of the gene.…”

Section: Phenotype Of E280 and Identification Of The Mutant Gene-mentioning

confidence: 80%

“…The mutant has been determined to have a point mutation in RIB3, a conserved gene of which the product, 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBP 1 synthase), catalyzes the first step in the riboflavin biosynthetic pathway (2). Complementation of aE280/U1 by RIB3 was unexpected in view of previous studies indicating that rib3 mutants require riboflavin for growth (3).…”

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confidence: 99%

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Yeast Dihydroxybutanone Phosphate Synthase, an Enzyme of the Riboflavin Biosynthetic Pathway, Has a Second Unrelated Function in Expression of Mitochondrial Respiration

Jin

Barrientos

Tzagoloff

2003

Journal of Biological Chemistry

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aE280/U1 is a pet mutant of Saccharomyces cerevisiae partially deficient in cytochromes a, a3, and cytochrome b. The ability of this mutant to respire is restored by RIB3, a gene previously shown to code for 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBP synthase), an enzyme of the riboflavin biosynthetic pathway. The sequences of RIB3 from wild type and aE280/U1 indicated a single base change resulting in an A137T substitution. The alanine 137 is a conserved residue located in a cavity on the surface of the protein distant from the active site and from the subunit interaction domain involved in homodimer formation. The respiratory defect elicited by this mutation cannot be explained by a flavin insufficiency based on the following evidence: 1) growth of the aE280/U1 on respiratory substrates is not rescued by exogenous riboflavin; 2) the levels of flavin nucleotides are not significantly different in the mutant and wild type. We proposed that in addition to its known function in riboflavin synthesis, RIB3 also functions in expression of mitochondrial respiration. Restoration by riboflavin of growth of a rib3 deletion mutant on glucose but not glycerol/ethanol also supported this conclusion. An antibody against the N-terminal half of DHBP synthase was used to study its subcellular distribution. Most of the protein was localized in the cytosolic fraction, but a small fraction was detected in the mitochondrial intermembrane space.Saccharomyces cerevisiae pet mutants have been used to study a broad range of problems related to mitochondrial function and biogenesis (1). Such mutants have been assigned to the following phenotypic classes based on their compositions of respiratory chain components: 1) mutants defective in individual carriers of the respiratory chain, 2) mutants having a normal set of respiratory enzymes (e.g. cytochrome spectra and ATPase), and 3) mutants with partial or severe pleiotropic deficiencies in respiratory chain components. Functional analysis of the latter is difficult because the phenotype fails to provide clues as to the nature of the biochemical lesion.In the present study we have characterized a pet mutant (aE280/U1) with partial pleiotropic defects in respiratory chain components. The mutant has been determined to have a point mutation in RIB3, a conserved gene of which the product, 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBP 1 synthase), catalyzes the first step in the riboflavin biosynthetic pathway (2). Complementation of aE280/U1 by RIB3 was unexpected in view of previous studies indicating that rib3 mutants require riboflavin for growth (3). The lack of correspondence in the phenotype of the rib3 point mutant and a mutant with a complete deletion of RIB3 prompted us to examine the biochemical properties of the mutant further. We present evidence that the phenotype of aE280/U1 is not related to a flavin nucleotide deficiency and propose that in addition to its involvement in riboflavin synthesis, DHBP synthase has another function essential for expression of respirati...

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Section: Fig 1 Phenotype Of E280supporting

confidence: 62%

Section: Phenotype Of E280 and Identification Of The Mutant Gene-mentioning

confidence: 80%

mentioning

confidence: 99%

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Yeast Dihydroxybutanone Phosphate Synthase, an Enzyme of the Riboflavin Biosynthetic Pathway, Has a Second Unrelated Function in Expression of Mitochondrial Respiration

Jin

Barrientos

Tzagoloff

2003

Journal of Biological Chemistry

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“…Bacher et al [15,16] found that riboflavin biosynthesis requires the precursor's guanosine 5′-triphosphate (GTP) and ribulose 5-phosphate. The first step of the GTP-dependent branch of the biosynthetic pathway is encoded by ribA in E. coli.…”

Section: Riboflavin Biosynthesismentioning

confidence: 99%

Biosynthesis of Vitamins by Probiotic Bacteria

Gu¹,

Li²

2016

Probiotics and Prebiotics in Human Nutrition and Health

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Vitamins are important micronutrients that are often precursors to enzymes, which all living cells require to perform biochemical reactions. However, humans cannot produce many vitamins, so they have to be externally obtained. Using vitamin-producing microorganisms could be an organic and marketable solution to using pseudo-vitamins that are chemically produced, and could allow for the production of foods with higher levels of vitamins that could reduce unwanted side effects. Probiotic bacteria, as well as commensal bacteria found in the human gut, such as Lactobacillus and Bifidobacterium, can de novo synthesize and supply vitamins to human body. In humans, members of the gut microbiota are able to synthesize vitamin K, as well as most of the water-soluble B vitamins, such as cobalamin, folates, pyridoxine, riboflavin, and thiamine.

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“…GTP cyclohydrolase II (EC 3.5.4.25) (GCHII) 3 catalyzes the first step in the riboflavin biosynthetic pathway, leading to the formation of flavin nucleotide coenzymes that are utilized for a range of enzymatic reactions (1). GCHII catalyzes the conversion of GTP to 2,5-diamino-6-␤-ribosyl-4(3H)-pyrimidinone 5Ј-phosphate (DARP) (Scheme 1), the substrate for diaminohydroxyphosphoribosylaminopyrimidine deaminase.…”

mentioning

confidence: 99%

GTP Cyclohydrolase II Structure and Mechanism

Ren

Kotaka

Lockyer

et al. 2005

Journal of Biological Chemistry

110

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GTP cyclohydrolase II converts GTP to 2,5-diamino-6-␤-ribosyl-4(3H)-pyrimidinone 5-phosphate, formate and pyrophosphate, the first step in riboflavin biosynthesis. The essential role of riboflavin in metabolism and the absence of GTP cyclohydrolase II in higher eukaryotes makes it a potential novel selective antimicrobial drug target. GTP cyclohydrolase II catalyzes a distinctive overall reaction from GTP cyclohydrolase I; the latter converts GTP to dihydroneopterin triphosphate, utilized in folate and tetrahydrobiopterin biosynthesis. The structure of GTP cyclohydrolase II determined at 1.54-Å resolution reveals both a different protein fold to GTP cyclohydrolase I and distinctive molecular recognition determinants for GTP; although in both enzymes there is a bound catalytic zinc. The GTP cyclohydrolase II⅐GMPCPP complex structure shows Arg 128 interacting with the ␣-phosphonate, and thus in the case of GTP, Arg 128 is positioned to act as the nucleophile for pyrophosphate release and formation of the proposed covalent guanylyl-GTP cyclohydrolase II intermediate. Tyr 105 is identified as playing a key role in GTP ring opening; it is hydrogen-bonded to the zinc-activated water molecule, the latter being positioned for nucleophilic attack on the guanine C-8 atom. Although GTP cyclohydrolase I and GTP cyclohydrolase II both use a zinc ion for the GTP ring opening and formate release, different residues are utilized in each case to catalyze this reaction step.GTP cyclohydrolase II (EC 3.5.4.25) (GCHII) 3 catalyzes the first step in the riboflavin biosynthetic pathway, leading to the formation of flavin nucleotide coenzymes that are utilized for a range of enzymatic reactions (1). GCHII catalyzes the conversion of GTP to 2,5-diamino-6-␤-ribosyl-4(3H)-pyrimidinone 5Ј-phosphate (DARP) (Scheme 1), the substrate for diaminohydroxyphosphoribosylaminopyrimidine deaminase. In certain bacteria, GCHII can form part of a bifunctional enzyme also containing 3,4,-dihydroxy-2-butanone-4-phosphate synthase. GCHII from Escherichia coli is encoded by the riba gene, giving a protein of 196 amino acids (2).The GCHII reaction involves a guanine ring-opening step and formate release, in common with the similarly named GTP cyclohydrolase I (EC 3.5.4.16) (GCHI), but other components of the two reactions catalyzed are rather different. GCHI does not hydrolyze pyrophosphate from GTP (unlike GCHII) but catalyzes a net expansion of the guanine base via a series of steps, starting with an opening of the imidazole ring and elimination of formate. An Amadori rearrangement involving the ribose is the next step, and finally ring closure yields a pteridine derivative, dihydroneopterin triphosphate (3). Dihydroneopterin triphosphate is utilized in microorganisms and plants as a folate precursor and in animals for the synthesis of tetrahydrobiopterin, an essential cofactor for many enzymes (4), including nitric-oxide synthases. Crystal structure data show that a zinc ion is present in bacterial and human GCHI, which catalyzes the guanine ring open...

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Biosynthesis of Vitamin B₂ (Riboflavin)

Cited by 261 publications

References 86 publications

Yeast Dihydroxybutanone Phosphate Synthase, an Enzyme of the Riboflavin Biosynthetic Pathway, Has a Second Unrelated Function in Expression of Mitochondrial Respiration

Yeast Dihydroxybutanone Phosphate Synthase, an Enzyme of the Riboflavin Biosynthetic Pathway, Has a Second Unrelated Function in Expression of Mitochondrial Respiration

Biosynthesis of Vitamins by Probiotic Bacteria

GTP Cyclohydrolase II Structure and Mechanism

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Biosynthesis of Vitamin B2 (Riboflavin)

Cited by 261 publications

References 86 publications

Yeast Dihydroxybutanone Phosphate Synthase, an Enzyme of the Riboflavin Biosynthetic Pathway, Has a Second Unrelated Function in Expression of Mitochondrial Respiration

Yeast Dihydroxybutanone Phosphate Synthase, an Enzyme of the Riboflavin Biosynthetic Pathway, Has a Second Unrelated Function in Expression of Mitochondrial Respiration

Biosynthesis of Vitamins by Probiotic Bacteria

GTP Cyclohydrolase II Structure and Mechanism

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Product

Resources

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Biosynthesis of Vitamin B₂ (Riboflavin)