Metabolic perturbation of an essential pathway: Evaluation of a glycine precursor of coenzyme A

Michael Rothmann, Minjin Kang, Reymundo Villa, Ioanna Ntai, James J. La Clair, Neil L. Kelleher, Eli Chapman, Michael D. Burkart

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Pantetheine and its corresponding disulfide pantethine play a key role in metabolism as building blocks of coenzyme A (CoA), an essential cofactor utilized in ∼4% of primary metabolism and central to fatty acid, polyketide, and nonribosomal peptide synthases. Using a combination of recombinant engineering and chemical synthesis, we show that the disulfide of N-pantoylglycyl-2-aminoethanethiol (GlyPan), with one fewer carbon than pantetheine, can rescue a mutant E. coli strain MG1655ΔpanC lacking a functional pantothenate synthetase. Using mass spectrometry, we show that the GlyPan variant is accepted by the downstream CoA biosynthetic machinery, ultimately being incorporated into essential acyl carrier proteins. These findings point to further flexibility in CoA-dependent pathways and offer the opportunity to incorporate orthogonal analogues.

Original languageEnglish (US)
Pages (from-to)5962-5965
Number of pages4
JournalJournal of the American Chemical Society
Volume135
Issue number16
DOIs
StatePublished - Apr 24 2013

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Rothmann, M., Kang, M., Villa, R., Ntai, I., La Clair, J. J., Kelleher, N. L., Chapman, E., & Burkart, M. D. (2013). Metabolic perturbation of an essential pathway: Evaluation of a glycine precursor of coenzyme A. Journal of the American Chemical Society, 135(16), 5962-5965. https://doi.org/10.1021/ja400795m