Pristinamycin IIA is a

macrolide antibiotic The Macrolides are a class of natural products that consist of a large macrocycle, macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-memb ...

. It is a member of the

streptogramin A Streptogramin A is a group of antibiotics within the larger family of antibiotics known as streptogramins. They are synthesized by the bacteria '' Streptomyces virginiae''. The streptogramin family of antibiotics consists of two distinct groups: ...

group of antibiotics and one component of

pristinamycin Pristinamycin ( INN), also spelled pristinamycine, is an antibiotic used primarily in the treatment of staphylococcal infections, and to a lesser extent streptococcal infections. It is a streptogramin group antibiotic, similar to virginiamycin, d ...

(the other being

pristinamycin IA Pristinamycin IA (Mikamycin B) is an antibiotic cyclic peptide. It is a member of the streptogramin B group of antibiotics and one component of pristinamycin (the other being pristinamycin IIA Pristinamycin IIA is a macrolide antibiotic. It is ...

). Pristinamycin IIA was first isolated from the Streptomyces virginiae, but has been isolated from other microorganisms and thus has been given a variety of other names such as Virginiamycin M1, Mikamycin A, and Streptogramin A. Pristinamycin IIA structure was determined by chemical and instrumental techniques, including X-ray crystallography. Pristinamycin IIA is of interest from a biosynthetic viewpoint because it contains the unusual dehydroproline and

oxazole Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak ...

ring systems. The only experimental evidence bearing on the formation of the

ring is found in work on the biosynthesis of the alkaloid annuloline. __TOC__

Biosynthesis

Pristinamycin IIA biosynthesis is presumed to proceed through the acetate pathway and was determined through the feeding of ³H and ¹³C precursors to Streptomyces virginiae strain PDT-30. When fed -¹³Cacetate the 13C

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...

Spectra showed signals corresponding to carbons 5, 9, 10a, 11, 13, and 15 seen in the biosynthesis scheme. In addition,

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

was found to donate its methyl group specifically to carbon-3 (seen in the biosynthesis scheme) by studies with L- ethyl-¹³Cmethionine. With this data and the known incorporation of

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

, and

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

into the antibiotic along with the assumption that carbon atoms 1, la, lb, and 2 are derived from

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotonat ...

isobutyric acid Isobutyric acid, also known as 2-methylpropanoic acid or isobutanoic acid, is a carboxylic acid with structural formula ( CH3)2CH COOH. It is an isomer of ''n''- butyric acid. It is classified as a short-chain fatty acid. Deprotonation or esterif ...

, allows for a tentative pathway for the biosynthesis of Pristinamycin IIA to be deduced.

References

Macrolide antibiotics Oxazoles {{antibiotic-stub

Biosynthesis

See also

References