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Bohemic acid is a mixture of chemical compounds which is obtained through fermentation by actinobacteria species in the Actinosporangium genus (Actinoplanaceae). The name honors the Puccini opera La Bohème and many individual components of the acid carry the names of characters from La Bohème. Most of those components are antitumor agents and anthracycline antibiotics active against Gram-positive bacteria.
Contents
Synthesis and fractions
Bohemic acid is produced through fermentation by an actinobacteria species in the Actinosporangium genus (Actinoplanaceae) in the order of Actinomycetales. Specifically, strain C36145 (ATCC 31127) produces bohemic acid. The acid can be extracted from the fermentation broth with methyl isobutyl ketone under neutral or slightly basic pH conditions, and the fats and oils are removed by washing with petroleum ether.
Chromatographical separation, in addition to the antibiotics pyrromycin and cinerubin A and B, reveals several individual components of bohemic acid, including alcindoromycin, bohemamine, collinemycin, marcellomycin, mimimycin, musettamycin, rudolphomycin and schaunardimycin. Their names originate from the characters Alcindoro, Colline, Marcello, Mimì, Musetta, Rodolfo (Rudolph) and Schaunard of the Puccini opera La Bohème, and the acid itself and the bohemamine component carry the name of the opera. The suffix -mycin is conventionally added to indicate antibiotics derived from actinobacteria or fungi.
Properties
The individual components of bohemic acid are orange-red solids, the color originating from an optical absorption band centered at about 490 nm. Marcellomycin and mimimycin, and collinemycin and musettamycin are stereoisomers, that is they have the same chemical compositions; however, one C-H and one COOCH3 group exchange places. Those two groups are attached to the same carbon atom of one carbon ring, they are marked by the blue star in their structure in the table (C-H group is not shown). Nearly all components of bohemic acid are anthracycline antibiotic agents active against Gram-positive bacteria, but not against Gram-negative bacteria, yeasts or fungi. The most potent component of the acid is rudolphomycin and the least potent is schaunardimycin, which is about 10 times weaker than musettamycin and 20 times weaker than marcellomycin. The original studies on the individual components of bohemic acid have tested them all for antitumor activity in mice, upon intraperitoneal injection. Furthermore, the antitumor pharmokinetics of marcellomycin in the human blood has been evaluated both in vitro and in vivo.
The median lethal dose (LD50) of marcellomycin depends strongly on the animal and varies from a few mg/kg of body weight (dogs) to 20 mg/kg (Suiss-Webster mice, intravenal injection), the major site of toxicity being the gastrointestinal tract. Bohemamine has several structural varieties and derivatives, such as bohemamine B (C14H20N2O3), bohemamine C (C14H21N2O3), and 5-chlorobohemamine C (C14H20ClN2O3). None of them showed antibiotic, antifungal or antitumor activity.
The bottom fragment of rudolphomycin is a cyclic (sugar) compound with a chemical formula C6H8NO3 and a proposed trivial name rednose.