Carriomycin

In the course of our microbial transformation study on erythromycin derivatives, Streptomyces hygroscopicus ATCC 31080, which produces a polyether antibiotic carriomycin, was found to transform erythromycin derivatives to their inactivated derivatives. The structures of inactivated derivatives prepared by enzyme reaction using the cell extract, UDP-glucose (or UDP-galactose) and Mg2+ (or Mn2+) were elucidated on the basis of analysis of thei spectral data to be the compounds glycosylated at C-2' of a desosamine moiety, indicating that the enzyme is a macrolide glycosyl transferase (MGT). The MGT activity of cell extract from S. antibioticus ATCC 11891, a producing organism of oleandomycin, could be distinguished from that of ATCC 31080, based on the ability to glycosylate tylosin. We examined 32 actinomycete strains producing such polyketides as macrolide and polyether antibiotics, and found that 15 strains of Streptomyces have macrolide glycosyl transferase activity. It suggests that the MGTs have been distributed among at least polyketide producing Streptomyces strains.

Protoplast regeneration carried out in a carriomycin producing organism, Streptomyces hygroscopicus 358 AV2, lose carriomycin productivity without loss of carriomycin-resistance and the ability of formation of aerial mycelium. Ethidium bromide treatment on the 358 AV2 strain generated a bald mutant that produced carriomycin and a new antibiotic curromycin. In some other media, however, the parent strain produced curromycin, indicating that the ethidium bromide treatment altered the regulation of antibiotic production. Ethidium bromide treatment on a protoplast-regenerated strain derived from the parent strain resulted in derivatives capable of producing carriomycin and curromycin. These strains were unstable and tended to lose the recovered antibiotic productivity easily.

Fast atom bombardment mass spectrometry (FAB MS) and fast atom bombardment mass spectrometry-mass spectrometry (FAB MS/MS) were used to study the monovalent glycoside polyether antibiotics maduramicin alpha, beta and delta and the maduramicin alpha salts, their derivatives and degradation products. Also, representative compounds from three major classes of polyether antibiotics were studied: the monovalent polyethers, nigericin and monensin A, the divalent polyether lasalocid A and the monovalent glycoside polyethers septamycin, BL580 delta, etheromycin and carriomycin. The respective FAB fragment and decomposition ions were correlated with the known structures. The FAB spectra of all the polyethers contained metal-adduct molecular ions. Protonated molecular ions were absent. All the polyethers having a beta-hemiketal carboxylic acid group produced an abundant ion, often the base peak of the spectra, 62 daltons less than the corresponding metal-adduct molecular ion. The gas phase mechanism proposed for the formation of this fragment ion is an unusual unimolecular reaction which is initiated by an intramolecular proton transfer from the carboxylic acid to the hydroxy group of the beta-hemiketal, and, then followed by the concerted losses of water and carbon dioxide to produce the corresponding polyether olefin.