The antibiotic activity of N-pentylpantothenamide results from its conversion to ethyldethia-coenzyme a, a coenzyme a antimetabolite. Academic Article uri icon

abstract

  • Pantothenic acid (vitamin B(5)) is the natural precursor of coenzyme A (CoA), an essential cofactor in all organisms. The pantothenic acid antimetabolite N-pentylpantothenamide inhibits the growth of Escherichia coli with a minimum inhibitory concentration of 2 microm. In this study, we examine the mechanism of this inhibition. Using the last five enzymes of the CoA biosynthetic pathway in E. coli we demonstrate that N-pentylpantothenamide does not inhibit the CoA biosynthetic enzymes but instead acts as an alternative substrate, forming the CoA analog ethyldethia-CoA. We show that N-pentylpantothenamide is converted to ethyldethia-CoA 10.5 times faster than CoA is biosynthesized from pantothenic acid, demonstrating that ethyldethia-CoA biosynthesis can effectively compete with CoA biosynthesis in the cell. We conclude that the mechanism of toxicity of N-pentylpantothenamide is most likely due to its biosynthetic conversion to the CoA analog ethyldethia-CoA, which may act as an inhibitor of CoA- and acetyl-CoA-utilizing enzymes.

published proceedings

  • J Biol Chem

altmetric score

  • 3

author list (cited authors)

  • Strauss, E., & Begley, T. P.

citation count

  • 99

complete list of authors

  • Strauss, Erick||Begley, Tadhg P

publication date

  • December 2002