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

3 Citations (Scopus)

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

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Coenzymes
Pantetheine
Coenzyme A
Glycine
Amino acids
pantothenate synthetase
Metabolism
Disulfides
Chemical Engineering
Acyl Carrier Protein
Polyketides
Cysteamine
Fatty acids
Escherichia coli
Peptides
Machinery
Mass spectrometry
Mass Spectrometry
Fatty Acids
Carbon

ASJC Scopus subject areas

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

Cite this

Rothmann, M., Kang, M., Villa, R., Ntai, I., La Clair, J. J., Kelleher, N. L., ... 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

Metabolic perturbation of an essential pathway : Evaluation of a glycine precursor of coenzyme A. / Rothmann, Michael; Kang, Minjin; Villa, Reymundo; Ntai, Ioanna; La Clair, James J.; Kelleher, Neil L.; Chapman, Eli; Burkart, Michael D.

In: Journal of the American Chemical Society, Vol. 135, No. 16, 24.04.2013, p. 5962-5965.

Research output: Contribution to journalArticle

Rothmann, M, Kang, M, Villa, R, Ntai, I, La Clair, JJ, Kelleher, NL, Chapman, E & Burkart, MD 2013, 'Metabolic perturbation of an essential pathway: Evaluation of a glycine precursor of coenzyme A', Journal of the American Chemical Society, vol. 135, no. 16, pp. 5962-5965. https://doi.org/10.1021/ja400795m
Rothmann, Michael ; Kang, Minjin ; Villa, Reymundo ; Ntai, Ioanna ; La Clair, James J. ; Kelleher, Neil L. ; Chapman, Eli ; Burkart, Michael D. / Metabolic perturbation of an essential pathway : Evaluation of a glycine precursor of coenzyme A. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 16. pp. 5962-5965.
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