Streptogramin B is a subgroup of the streptogramin

Streptogramin

Streptogramins are a class of antibiotics.Streptogramins are effective in the treatment of vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus , two of the most rapidly-growing strains of multidrug-resistant bacteria...

 antibiotics family. These natural products are cyclic hexa- or hepta depsipeptides produced by various members of the genus of bacteria Streptomyces

Streptomyces

Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...

. Many of the members of the streptogramins reported in the literature have the same structure and different names; for example, pristinamycin IA

Pristinamycin IA

Pristinamycin IA is an antibiotic cyclic peptide. It is a member of the streptogramin B group of antibiotics and one component of pristinamycin ....

 = vernamycin Bα = mikamycin B = osteogrycin B.

Biosynthesis

The biosynthesis of streptogramin B is carried out by large multifunctional enzymes called non-ribosomal peptide synthetases (NRPS). In the NRPS system, each amino acid is activated as an aminoacyladenylate and is linked to the enzyme as a thioester with a phosphopantetheinyl group. An elongation reaction then occurs by transferring the activated carboxyl to the amino group in the next amino acid, thus executing the N-to-C stepwise condensation.

NRPSs contain several modules on a single polypeptide. Each of these modules can catalyze activation, condensation and a modification reaction specific to one kind of amino acid. A typical elongation module consists of an adenylation domain (A), a peptidyl carrier protein domain (PCP) and a condensation domain

Condensation domain

In molecular biology, the condensation domain is a protein domain found in many multi-domain enzymes which synthesise peptide antibiotics. This domain catalyses a condensation reaction to form peptide bonds in non-ribosomal peptide biosynthesis. It is usually found to the carboxy side of a...

 (C). Some other domains may be present that are responsible for modifications to the residues, such as epimerization domain (E) and N-methyltransferase domain (MT). The domain responsible for the termination is the thioesterase domain (TE) located in the final module.

Amino Acid Composition

The general amino acid composition of streptogramin B consists of: 3-hydroxypicolinic acid, L-threonine, D-aminobutyric acid, L-proline, 4-N,N-(dimethylamino)-L-phenylalanine, 4-oxo-L-pipecolic acid and phenylglycine.

Modular Arrangement

Mechanism of Action

Streptogramins A and B synergically inhibit bacterial cell growth by inhibiting protein synthesis, but separately they are bacteriostatic. The molecular target of streptogramins is the 23S rRNA. Both streptogramin A and B bind to the P binding site of the 50S ribosome subunit. The type A streptogramin binding causes a conformational change to the 50S subunit, which increases the activity of the type B by a 100-fold. Streptogramin B prevents the elongation of protein chains and causes the release of incomplete peptides.

Clinical use

The streptogramin antibiotics were identified almost 50 years ago, but have only recently found clinical use as a consequence of the increase in multidrug-resistant bacteria. They present poor solubility in aqueous solution, and this has limited their clinical use; however, the natural products still find use as feed additives in agriculture.

Medicinal chemists at Rhône-Poulenc worked in the preparation of semi-synthetic, water-soluble, derivatives of pristinamycin IA

Pristinamycin IA

Pristinamycin IA is an antibiotic cyclic peptide. It is a member of the streptogramin B group of antibiotics and one component of pristinamycin ....

 (B type streptogramin) and pristinamycin IIA

Pristinamycin IIA

Pristinamycin IIA is a macrolide antibiotic. It is a member of the streptogramin A group of antibiotics and one component of pristinamycin ....

 (A type streptogramin) giving rise to quinupristin and dalfopristin

Dalfopristin

Dalfopristin is a streptogramin antibiotic derived from pristinamycin IIA. The combination quinupristin/dalfopristin, in a weight-to-weight ratio of 30% quinupristin to 70% dalfopristin, is used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....

, respectively, which, when administered in a 3:7 ratio, comprise the 1999 FDA approved drug Synercid.