Biosynthesis of the lincomycins. 1. Studies using stable isotopes on the biosynthesis of the propyl- and ethyl-L-hygric acid moieties of lincomycins A and B

Nanda M. Brahme, Jose E. Gonzalez, Jim P. Rolls, Ed J. Hessler, Steve Mizsak, Laurence Hurley

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The biosynthesis of the propyl-L-hygric acid and ethyl-L-hygric acid moieties of lincomycins A and B has been examined by using deuterated and carbon-13 labeled precursors in combination with carbon-13 NMR and mass spectral analysis. The results, using specifically deuterated tyrosine, DOPA, and methionine, demonstrate that tyrosine is converted via DOPA to an intermediate that undergoes aromatic ring cleavage most probably via a 2,3-extradiol cleavage reaction. An experiment using D-(13C6)glucose in combination with analysis of the 13C-13C spin-coupling patterns in lincomycin A and propyl-L-hygric acid permits the determination of those carbon atoms that remain together during the biosynthesis of lincomycin A. Glucose is converted via glycolysis and the hexose monophosphate shunt to phosphoenolpyruvate and erythrose 4-phosphate, respectively, which are in turn converted via the shikimic acid pathway to tyrosine and hence into DOPA. The subsequent reactions after DOPA are consistent with the 2,3-extradiol cleavage pathway and an addition of a C-1 unit from methionine to give rise to the terminal methyl group of the propyl side chain. These results are now consistent with those obtained for the C2- and C3-proline moieties found in anthramycin, tomaymycin, and sibiromycin that are also biosynthetically derived from tyrosine.

Original languageEnglish (US)
Pages (from-to)7873-7878
Number of pages6
JournalJournal of the American Chemical Society
Volume106
Issue number25
StatePublished - 1984
Externally publishedYes

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Lincomycin
Biosynthesis
Isotopes
Tyrosine
Acids
Carbon
Methionine
Glucose
Anthramycin
Shikimic Acid
Pentose Phosphate Pathway
Phosphoenolpyruvate
Hexoses
Glycolysis
Proline
Spectrum analysis
Phosphates
Nuclear magnetic resonance
Atoms
lincomycin-B

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Biosynthesis of the lincomycins. 1. Studies using stable isotopes on the biosynthesis of the propyl- and ethyl-L-hygric acid moieties of lincomycins A and B. / Brahme, Nanda M.; Gonzalez, Jose E.; Rolls, Jim P.; Hessler, Ed J.; Mizsak, Steve; Hurley, Laurence.

In: Journal of the American Chemical Society, Vol. 106, No. 25, 1984, p. 7873-7878.

Research output: Contribution to journalArticle

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