Biosynthesis of pantothenate

Webb, Michael E.; Smith, Alison G.; Abell, Chris

doi:10.1039/b316419p

Cited by 138 publications

(112 citation statements)

References 161 publications

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“…It is not clear what molecule this mutant acquired from the host or where it acquired it to satisfy its pantothenate requirement. Given that mice have a blood plasma pantothenate level of 20 M while humans have only 2 to 4 M, it is possible that an F. tularensis pantothenate synthesis mutant could be attenuated in humans but not mice (45). It is possible that mice have excess pantothenate in their bloodstream, considering their diet is supplemented with pantothenate in addition to that naturally acquired from their gut flora.…”

Section: Discussionmentioning

confidence: 99%

PanG, a New Ketopantoate Reductase Involved in Pantothenate Synthesis

Miller

LoVullo

Kijek

et al. 2012

Journal of Bacteriology

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Pantothenate, commonly referred to as vitamin B 5 , is an essential molecule in the metabolism of living organisms and forms the core of coenzyme A. Unlike humans, some bacteria and plants are capable of de novo biosynthesis of pantothenate, making this pathway a potential target for drug development. Francisella tularensis subsp. tularensis Schu S4 is a zoonotic bacterial pathogen that is able to synthesize pantothenate but is lacking the known ketopantoate reductase (KPR) genes, panE and ilvC, found in the canonical Escherichia coli pathway. Described herein is a gene encoding a novel KPR, for which we propose the name panG (FTT1388), which is conserved in all sequenced Francisella species and is the sole KPR in Schu S4. Homologs of this KPR are present in other pathogenic bacteria such as Enterococcus faecalis, Coxiella burnetii, and Clostridium difficile. Both the homologous gene from E. faecalis V583 (EF1861) and E. coli panE functionally complemented Francisella novicida lacking any KPR. Furthermore, panG from F. novicida can complement an E. coli KPR double mutant. A Schu S4 ⌬panG strain is a pantothenate auxotroph and was genetically and chemically complemented with panG in trans or with the addition of pantolactone. There was no virulence defect in the Schu S4 ⌬panG strain compared to the wild type in a mouse model of pneumonic tularemia. In summary, we characterized the pantothenate pathway in Francisella novicida and F. tularensis and identified an unknown and previously uncharacterized KPR that can convert 2-dehydropantoate to pantoate, PanG.

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Section: Discussionmentioning

confidence: 99%

PanG, a New Ketopantoate Reductase Involved in Pantothenate Synthesis

Miller

LoVullo

Kijek

et al. 2012

Journal of Bacteriology

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“…6). This finding is particularly interesting considering that the biosyntheses of Val, Leu, and pantothenate share ␣-ketoisovalerate as a common precursor (110). One possible explanation for the use of this type of regulation for the pantothenate (pan) biosynthetic genes would include the sensing of a metabolic stage requiring an increased synthesis of the BCAAs and their precursors.…”

Section: Pathways For Synthesis Of the Sulfur-containing Amino Acids mentioning

confidence: 99%

Biochemical Features and Functional Implications of the RNA-Based T-Box Regulatory Mechanism

Gutiérrez-Preciado

Henkin

Grundy

et al. 2009

Microbiol Mol Biol Rev

140

230

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SUMMARY The T-box mechanism is a common regulatory strategy used for modulating the expression of genes of amino acid metabolism-related operons in gram-positive bacteria, especially members of the Firmicutes. T-box regulation is usually based on a transcription attenuation mechanism in which an interaction between a specific uncharged tRNA and the 5′ region of the transcript stabilizes an antiterminator structure in preference to a terminator structure, thereby preventing transcription termination. Although single T-box regulatory elements are common, double or triple T-box arrangements are also observed, expanding the regulatory range of these elements. In the present study, we predict the functional implications of T-box regulation in genes encoding aminoacyl-tRNA synthetases, proteins of amino acid biosynthetic pathways, transporters, and regulatory proteins. We also consider the global impact of the use of this regulatory mechanism on cell physiology. Novel biochemical relationships between regulated genes and their corresponding metabolic pathways were revealed. Some of the genes identified, such as the quorum-sensing gene luxS, in members of the Lactobacillaceae were not previously predicted to be regulated by the T-box mechanism. Our analyses also predict an imbalance in tRNA sensing during the regulation of operons containing multiple aminoacyl-tRNA synthetase genes or biosynthetic genes involved in pathways common to more than one amino acid. Based on the distribution of T-box regulatory elements, we propose that this regulatory mechanism originated in a common ancestor of members of the Firmicutes, Chloroflexi, Deinococcus-Thermus group, and Actinobacteria and was transferred into the Deltaproteobacteria by horizontal gene transfer.

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“…Pantothenate provides the 49-phosphopantetheine moiety in CoA and is an acyl carrier involved in lipid biosynthesis and catabolism as well as in pyruvate decarboxylase activity (Webb et al, 2004). No known disease has been associated with a lack of this compound, as it is found in small amounts in many foods and its content is particularly high in human foods such as wholegrain cereals, legumes, eggs, meat, and avocado (Table 3).…”

Section: Vitamin B 5 (Pantothenate)mentioning

confidence: 99%

Vitamin Deficiencies in Humans: Can Plant Science Help?

et al. 2012

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The term vitamin describes a small group of organic compounds that are absolutely required in the human diet. Although for the most part, dependency criteria are met in developed countries through balanced diets, this is not the case for the five billion people in developing countries who depend predominantly on a single staple crop for survival. Thus, providing a more balanced vitamin intake from high-quality food remains one of the grandest challenges for global human nutrition in the coming decade(s). Here, we describe the known importance of vitamins in human health and current knowledge on their metabolism in plants. Deficits in developing countries are a combined consequence of a paucity of specific vitamins in major food staple crops, losses during crop processing, and/or overreliance on a single species as a primary food source. We discuss the role that plant science can play in addressing this problem and review successful engineering of vitamin pathways. We conclude that while considerable advances have been made in understanding vitamin metabolic pathways in plants, more cross-disciplinary approaches must be adopted to provide adequate levels of all vitamins in the major staple crops to eradicate vitamin deficiencies from the global population.

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Biosynthesis of pantothenate

Cited by 138 publications

References 161 publications

PanG, a New Ketopantoate Reductase Involved in Pantothenate Synthesis

PanG, a New Ketopantoate Reductase Involved in Pantothenate Synthesis

Biochemical Features and Functional Implications of the RNA-Based T-Box Regulatory Mechanism

Vitamin Deficiencies in Humans: Can Plant Science Help?

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