Metabolic Perturbation of an Essential Pathway: Evaluation of a Glycine Precursor of Coenzyme A
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- 作者：Michael Rothmann ; MinJin Kang ; Reymundo Villa ; Ioanna Ntai ; James J. La Clair ; Neil L. Kelleher ; Eli Chapman ; Michael D. Burkart
- 刊名：The Journal of the American Chemical Society
- 出版年：2013
- 出版时间：April 24, 2013
- 年：2013
- 卷：135
- 期：16
- 页码：5962-5965
- 全文大小：320K
- 年卷期：v.135,no.16(April 24, 2013)
- ISSN：1520-5126
文摘
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 MG1655螖panC 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.