Biosynthesis of the lincomycins. 2. Studies using stable isotopes on the biosynthesis of methylthiolincosaminide moiety of lincomycin A

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Lincomycin is an antibiotic produced by Streptomyces lincolnensis and consists of a unique aminooctose moiety, α-methylthiolincosaminide (MTL), attached via an amide linkage to a propylhygric acid unit. The biosynthesis of the MTL moiety of lincomycin has been investigated by using both specifically carbon-13 labeled substrates and uniformly carbon-13 labeled D-glucose. In the latter case 13C-13C spin coupling patterns in lincomycin and MTL were used to determine those carbon atoms from glucose that remained intact during their conversion to the antibiotic. By combination of the biosynthetic information obtained from the 13C-13C spin coupling patterns with that from those carbon atoms in MTL which were enriched from carbon-13 specifically labeled molecules, conclusions can be drawn about likely pathways and intermediates between glucose and MTL. The C8-carbon skeleton of MTL is assembled through condensation of a pentose unit (C5) and a C3 unit. The C5 unit can be assembled in two ways. Either it is derived from glucose via the hexose monophosphate shunt (HMPS) as an intact unit or it is assembled from condensation of a C3 unit (glyceraldehyde 3-phosphate) with a C2-unit donor such as sedoheptulose 7-phosphate (SH7P) via a transketolase reaction. The C3 unit, which combines with the C5 unit, is likely contributed from a suitable donor molecule such as SH7P via a transaldolase reaction. Dependent upon the origin of the C3-unit donor, this unit may consist either of an intact C3 unit or a C2 unit combined with a C1 unit. The octase produced from condensation of a C5 unit and a C3 unit can then be converted by unexceptional means to MTL.

Original languageEnglish (US)
Pages (from-to)7878-7883
Number of pages6
JournalJournal of the American Chemical Society
Volume106
Issue number25
StatePublished - 1984
Externally publishedYes

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Lincomycin
Biosynthesis
Isotopes
Carbon
Glucose
Condensation
Phosphates
Antibiotics
Transaldolase
Glyceraldehyde 3-Phosphate
Transketolase
Anti-Bacterial Agents
Pentoses
Pentose Phosphate Pathway
Atoms
Molecules
Hexoses
Streptomyces
Amides
Skeleton

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Biosynthesis of the lincomycins. 2. Studies using stable isotopes on the biosynthesis of methylthiolincosaminide moiety of lincomycin A. / Brahme, Nanda M.; Gonzalez, Jose E.; Mizsak, Steve; Rolls, Jim R.; Hessler, Ed J.; Hurley, Laurence.

In: Journal of the American Chemical Society, Vol. 106, No. 25, 1984, p. 7878-7883.

Research output: Contribution to journalArticle

Brahme, Nanda M. ; Gonzalez, Jose E. ; Mizsak, Steve ; Rolls, Jim R. ; Hessler, Ed J. ; Hurley, Laurence. / Biosynthesis of the lincomycins. 2. Studies using stable isotopes on the biosynthesis of methylthiolincosaminide moiety of lincomycin A. In: Journal of the American Chemical Society. 1984 ; Vol. 106, No. 25. pp. 7878-7883.
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