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Salvage of Coenzyme A breakdown products by the STM4195 gene product in Salmonella enterica (LB276)
Author(s) -
Ernst Dustin,
Downs Diana
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb276
Subject(s) - coenzyme a , biosynthesis , biochemistry , salmonella enterica , acyl carrier protein , metabolic pathway , cofactor , chemistry , metabolic engineering , metabolite , gene , biology , enzyme , escherichia coli , reductase
Coenzyme A (CoA) is an essential cofactor required in all living organisms, where it functions primarily as an acyl‐group carrier and activator of carbonyl groups. The biosynthetic pathway generating CoA from pantothenic acid is universally conserved in prokaryotes and eukaryotes. Pantothenate is generated in a pathway that culminates in the condensation of pantoate and β‐alanine. Animals are unable to synthesize pantothenate and must salvage it, or other metabolic intermediates, to generate CoA. In Salmonella enterica, intermediates up to and including pantothenate can be fed exogenously to support CoA biosynthesis. Previous studies have shown that intermediates in CoA biosynthesis beyond pantothenate are not readily salvaged by S. enterica. The work here found that a degradation product of Coenzyme A, derived from boiling CoA, can bypass a genetic block in the final step of pantothenate biosynthesis. The data also showed that the STM4195 gene product is required to salvage this unknown metabolite, and also transports pantothenate precursors, ketopantoate and pantoate. STM4195 is a member of the sodium bile acid symporter family (SBF) of proteins. HPLC separation of a preparation of boiled CoA defined a peak with biological activity, and mass spectrometry and NMR approaches are being used to identify the compound. The results herein provide the first evidence for an active mechanism to transport ketopantoate and pantoate, and further demonstrate a role for STM4195 in the salvage of a unique CoA breakdown product. Grant Funding Source : Supported by NIH GM095837