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. Macrol ...

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

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

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 Pfizer ...

. 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 f ...

, 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 is ...

, and

ammonium dihydrogen phosphate Ammonium dihydrogen phosphate (ADP), also known as monoammonium phosphate (MAP) is a chemical compound with the chemical formula (NH4)(H2PO4). ADP is a major ingredient of agricultural fertilizers and some fire extinguishers. It also has sign ...

have the same effect on the production of carbomycin. The addition of the organic salts

sodium acetate Sodium acetate, CH3COONa, also abbreviated Na O Ac, is the sodium salt of acetic acid. This colorless deliquescent salt has a wide range of uses. Applications Biotechnological Sodium acetate is used as the carbon source for culturing bacteria ...

and

sodium tartrate Sodium tartrate (Na2C4H4O6) is a salt used as an emulsifier and a binding agent in food products such as jellies, margarine, and sausage casings. As a food additive, it is known by the E number E335. Because its crystal structure captures a ve ...

also increases the yield of the antibiotic. Studies of the chemical degradation of carbomycin and comparison of molar activities of

propionate Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a liqu ...

-labeled carbomycins and their degradation products suggest that the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

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 (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

units and one propionate unit with the branching

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

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 duri ...

. 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 ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultati ...

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 follo ...

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. Complicatio ...

. In 1954, carbomycin was found to be an effective treatment for

granuloma inguinale Granuloma inguinale is a bacterial disease caused by ''Klebsiella granulomatis'' (formerly known as ''Calymmatobacterium granulomatis'') characterized by genital ulcers. It is endemic in many less-developed regions. It is also known as donovano ...

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 ac ...

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 Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

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

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

, 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. A ...

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

References

{{GlycopeptideAntiBio Antibiotics Macrolide antibiotics Epoxides