Title: PanG, a new ketopantoate reductase involved in pantothenate synthesis Authors
|Miller, Cheryl -|
|Kijek, Todd -|
|Fuller, James -|
|Brunton, Jason -|
|Steele, Shaun -|
|Taft-Benz, Sharon -|
|Richardson, Anthony -|
|Kawula, Thomas -|
Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 6, 2012
Publication Date: March 1, 2013
Citation: Miller, C.N., Lovullo, E.D., Kijek, T.M., Fuller, J.R., Brunton, J.C., Steele, S.P., Taft-Benz, S.A., Richardson, A.R., Kawula, T.H. 2013. PanG, a new ketopantoate reductase involved in pantothenate synthesis. Journal of Bacteriology. 195(5):965-976. Interpretive Summary: The production of vitamin B5, pantothenate, is an essential molecule necessary for the metabolism of living organisms. Scientists at The University of North Carolina, Chapel Hill, North Carolina and the USDA-Agriculture Research Service, Center for Medical, Agricultural and Veterinary Entomology, Gainesville, Florida, identified the gene for a novel enzyme ketopantoate reductase (KPR) critical for the production of pantothenate in bacteria. Deletion of the KPR gene eliminates vitamin B5 production and creates a nutritional requirement for the mutant bacteria. However, the KPR deletion does not affect virulence of the bacteria when they are provided vitamin B5.
Technical Abstract: Pantothenate, commonly referred to as vitamin B5, 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 subspecies 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) that 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 the 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 as compared to wild-type in a mouse model of pneumonic tularemia. In summary, we characterized the pantothenate pathway in Francisella novicida and tularensis and identified an unknown and previously uncharacterized KPR that can convert 2-28 dehydropantoate to pantoate, PanG.