Carbomycin, also known as magnamycin, is a colorless, optically active crystalline

macrolide The Macrolides are a class of natural products that consist of a large 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-membered. M ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...

with the molecular formula C₄₂ H₆₇ N O₁₆. It is derived from the bacterium ''

Streptomyces halstedii ''Streptomyces halstedii'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from deeper soil layers. ''Streptomyces halstedii'' produces magnamycin B, vicenistatin deltamycin A2, deltamycin A3, bafilomycin B1 ...

'' and active in inhibiting the growth of

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

and "certain

Mycoplasma ''Mycoplasma'' is a genus of bacteria that, like the other members of the class '' Mollicutes'', lack a cell wall around their cell membranes. Peptidoglycan ( murein) is absent. This characteristic makes them naturally resistant to antibiotic ...

strains." Its structure was first proposed by Robert Woodward in 1957 and was subsequently corrected in 1965.

Synthesis

The discovery of carbomycin was first reported by Fred W. Tanner Jr. of

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfize ...

. Carbomycin can be isolated from ''Streptomyces halstedii'' via extraction from a fermentation broth and purified through crystallization from alcohol-water mixtures. Carbomycin can be further purified with the use of preparative

thin-layer chromatography Thin-layer chromatography (TLC) is a chromatography technique used to separate non-volatile mixtures. Thin-layer chromatography is performed on a sheet of an inert substrate such as glass, plastic, or aluminium foil, which is coated with a t ...

. The most efficient solvent is one consisting of ethanol-hexane-water in 90-10-0.15 volume ratio. In the biosynthesis of carbomycin by ''Streptomyces halstedii'', when soybean meal is used to ferment the antibiotic, the addition of several substances can increase the yield of carbomycin. When

blackstrap molasses Molasses () is a viscous substance resulting from refining sugarcane or sugar beets into sugar. Molasses varies in the amount of sugar, method of extraction and age of the plant. Sugarcane molasses is primarily used to sweeten and flavour foods. ...

, a carbon source, is added, an increased yield is observed. Nitrogen sources ammonium chloride,

ammonium nitrate Ammonium nitrate is a chemical compound with the chemical formula . It is a white crystalline salt consisting of ions of ammonium and nitrate. It is highly soluble in water and hygroscopic as a solid, although it does not form hydrates. It ...

, and ammonium dihydrogen phosphate have the same effect on the production of carbomycin. The addition of the organic salts sodium acetate and sodium tartrate also increases the yield of the antibiotic. Studies of the chemical degradation of carbomycin and comparison of molar activities of propionate-labeled carbomycins and their degradation products suggest that the biosynthesis of carbomycin by ''Streptomyces halstedii'' include the synthesis of the

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

backbone from eight

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

units and one propionate unit with the branching methyl group deriving from C-3 of propionate.

Medical use

As carbomycin is not a strong antibiotic, it is not used extensively and is considered a minor antibiotic; it is most effective when used in combination with other drugs. The range of activity of carbomycin is similar to that of

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used du ...

. In testing the response of 74 strains of bacteria, their susceptibility across carbomycin and

was consistent. However, a higher concentration of carbomycin is needed to achieve the same effect as that of erythromycin. The effectiveness of carbomycin as an antibiotic varies. When used to treat 45 patients with pneumonia, carbomycin was as effective as other antibiotics for six patients. Two developed meningitis, while, for twelve patients, it was necessary that the use of carbomycin in treatment be replaced with

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

. Carbomycin has been successful in treating neither staphylococcal

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is foll ...

nor

bacterial endocarditis Infective endocarditis is an infection of the inner surface of the heart, usually the valves. Signs and symptoms may include fever, small areas of bleeding into the skin, heart murmur, feeling tired, and low red blood cell count. Complicati ...

. In 1954, carbomycin was found to be an effective treatment for granuloma inguinale by Harry M. Robinson and Morris M. Cohen. However, complete healing from the condition depends on the severity and duration of the condition. There were no adverse reactions found to be associated with the use of carbomycin.

Mode of action

Carbomycin stimulates the "accumulation of peptidyl-

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino a ...

in cells at the nonpermissive temperature" of 40˚C in '' E. coli'' and thereby inhibits

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...

. Carbomycin is able to inhibit protein synthesis by stimulating the dissociation of peptidyl-tRNA from the ribosome, inhibiting the nascent

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

chain from passing through the exit tunnel and out of the ribosome.

References

{{GlycopeptideAntiBio Antibiotics Macrolide antibiotics Epoxides