The riboflavin kinase encoding generibRofBacillus subtilisis a part of a 10 kb operon, which is negatively regulated by theyrzCgene product

Solovieva, I. M.; Кренева, Р. А.; Lopes, Liubov Errais; Перумов, Д. А.

doi:10.1016/j.femsle.2004.11.038

Cited by 16 publications

(20 citation statements)

References 20 publications

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“…A LysR homolog, encoded by a divergently oriented ytlI gene, exerts positive control over the ytmI operon (8), and Spx indirectly regulates ytmI expression by controlling the expression of the ytlI gene in medium containing sulfate. Recently, it was also reported that CymR is a negative regulator of the ytmI operon and ytlI gene expression (8,14,42). To investigate the role of CymR as a negative regulator for ytlI expression, we expressed the ytlIЈ-lacZ fusion (13) in wild-type (ORB5691), spx (ORB4871), and cymR mutant (ORB5733) strains.…”

Section: Resultsmentioning

confidence: 99%

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

et al. 2006

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Spx is a global transcriptional regulator of the oxidative stress response in Bacillus subtilis. Its target is RNA polymerase, where it contacts the ␣ subunit C-terminal domain. Recently, evidence was presented that Spx participates in sulfate-dependent control of organosulfur utilization operons, including the ytmI, yxeI, ssu, and yrrT operons. The yrrT operon includes the genes that function in cysteine synthesis from S-adenosylmethionine through intermediates S-adenosylhomocysteine, ribosylhomocysteine, homocysteine, and cystathionine. These operons are also negatively controlled by CymR, the repressor of cysteine biosynthesis operons. All of the operons are repressed in media containing cysteine or sulfate but are derepressed in medium containing the alternative sulfur source, methionine. Spx was found to negatively control the expression of these operons in sulfate medium, in part, by stimulating the expression of the cymR gene. In addition, microarray analysis, monitoring of yrrT-lacZ fusion expression, and in vitro transcription studies indicate that Spx directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source. These experiments have uncovered additional roles for Spx in the control of gene expression during unperturbed, steadystate growth.The global regulator Spx of Bacillus subtilis functions in the oxidative stress response by activating transcription of genes that function in thiol homeostasis (33,34,49). In this capacity, it is required for the transcriptional activation of the thioredoxin (trxA) and thioredoxin reductase (trxB) genes in response to disulfide stress. It also represses genes that function in a variety of metabolic and developmental pathways (34,35). The activity and synthesis of Spx are stimulated when cells undergo accelerated disulfide generation resulting from encounters with toxic oxidants. The accumulated Spx interacts with RNA polymerase (RNAP) in part by contacting residues of the alpha subunit C-terminal domain (CTD), while showing no sequence-specific DNA-binding activity (36). An important feature of Spx is the N-terminal CxxC redox disulfide motif that controls Spx activity. Transcriptional activation from the trxA and trxB promoters requires that the two cysteines be in the oxidized, disulfide state. The presence of a reductant that converts the cysteines to the thiol state results in loss of transcription-stimulating activity (33). It is currently not known how the interaction of oxidized Spx protein with RNA polymerase activates transcription at promoters under Spx positive control.In addition to its role in oxidative stress, recent studies indicate that Spx functions as a regulator of gene expression in cells undergoing steady-state growth. Spx was found to negatively affect the transcription of genes that function in the utilization of organosulfur compounds as alternative sources of sulfur (13). Such operons are repressed in minimal glucose media containing either of the two preferred sulfur sources, sulfate and cys...

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Section: Resultsmentioning

confidence: 99%

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

et al. 2006

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“…The structures of S. pombe and human RF kinases showed a novel family of phosphoryl-transferring enzymes (26,211). The role of monofunctional B. subtilis RF kinase in FMN synthesis in vivo has yet to be clarified (177,457,458). In addition to monofunctional RF kinases, bifunctional RF kinase/FAD synthetase is the main enzyme involved in eubacterial flavin nucleotide biosynthesis (101,280,286,320).…”

Section: Riboflavin Kinasementioning

confidence: 99%

Genetic Control of Biosynthesis and Transport of Riboflavin and Flavin Nucleotides and Construction of Robust Biotechnological Producers

Abbas

Sibirny

2011

Microbiol Mol Biol Rev

316

272

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SUMMARY Riboflavin [7,8-dimethyl-10-(1′- d -ribityl)isoalloxazine, vitamin B 2 ] is an obligatory component of human and animal diets, as it serves as the precursor of flavin coenzymes, flavin mononucleotide, and flavin adenine dinucleotide, which are involved in oxidative metabolism and other processes. Commercially produced riboflavin is used in agriculture, medicine, and the food industry. Riboflavin synthesis starts from GTP and ribulose-5-phosphate and proceeds through pyrimidine and pteridine intermediates. Flavin nucleotides are synthesized in two consecutive reactions from riboflavin. Some microorganisms and all animal cells are capable of riboflavin uptake, whereas many microorganisms have distinct systems for riboflavin excretion to the medium. Regulation of riboflavin synthesis in bacteria occurs by repression at the transcriptional level by flavin mononucleotide, which binds to nascent noncoding mRNA and blocks further transcription (named the riboswitch). In flavinogenic molds, riboflavin overproduction starts at the stationary phase and is accompanied by derepression of enzymes involved in riboflavin synthesis, sporulation, and mycelial lysis. In flavinogenic yeasts, transcriptional repression of riboflavin synthesis is exerted by iron ions and not by flavins. The putative transcription factor encoded by SEF1 is somehow involved in this regulation. Most commercial riboflavin is currently produced or was produced earlier by microbial synthesis using special selected strains of Bacillus subtilis , Ashbya gossypii , and Candida famata . Whereas earlier RF overproducers were isolated by classical selection, current producers of riboflavin and flavin nucleotides have been developed using modern approaches of metabolic engineering that involve overexpression of structural and regulatory genes of the RF biosynthetic pathway as well as genes involved in the overproduction of the purine precursor of riboflavin, GTP.

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“…According to Solovieva et al (2005), the expression of the ribR gene suppresses the riboflavin overproduction phenotype of Bacillus subtilis ribC mutant strains, which is a result of the strongly reduced flavokinase activity of the riboflavin kinase/FAD synthetase encoded by ribC. Sauer et al (1998) ) of inosine or guanosine (Debabov, 1982).…”

Section: Theoretical Backgroundmentioning

confidence: 99%

Scale-down and parallel operation of the riboflavin production process with Bacillus subtilis

Knorr

Schlieker²,

Hohmann³

et al. 2007

Biochemical Engineering Journal

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The riboflavin kinase encoding generibRofBacillus subtilisis a part of a 10 kb operon, which is negatively regulated by theyrzCgene product

Cited by 16 publications

References 20 publications

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

Genetic Control of Biosynthesis and Transport of Riboflavin and Flavin Nucleotides and Construction of Robust Biotechnological Producers

Scale-down and parallel operation of the riboflavin production process with Bacillus subtilis

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