candicidin and 4-aminoacetophenone

A high-performance liquid chromatographic (HPLC) method for the determination of the aromaticity of heptaene polyene antibiotics has been developed. The released aromatic moiety of the heptaene polyenes aureofungin, candicidin, candimycin, hamycin and trichomycin was assayed after alkaline hydrolysis. The presence of p-aminoacetophenone (PAAP) and N-methyl-p-aminoacetophenone (N-methyl-PAAP) in the hydrolysates was determined by HPLC, HPLC-mass spectrometry (HPLC-MS) and gas chromatography-MS (GC-MS). Candicidin and hamycin contained only the PAAP residue; aureofungin contained both PAAP and N-methyl-PAAP. Trichomycin contained PAAP and also some unknown component of molecular weight 179. The aromatic nature of the individual components of the heptaene complex was demonstrated using radioactivity flow detection for the determination of the incorporation of [14C]-p-aminobenzoic acid to individual candicidin components. Ammonia chemical ionization MS was successfully used for the GC-MS identification of the acetylated mycosamine moiety of heptaenes.

Topics: 4-Aminobenzoic Acid; Acetophenones; Antifungal Agents; Candicidin; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Hexosamines; Mass Spectrometry; Polyenes; Spectrophotometry, Ultraviolet; Streptomyces griseus

The effect of p-aminobenzoic acid on the biosynthesis of levorin was studied. It was shown that in the presence of exogenic p-aminobenzoic acid the antibiotic activity increased by 11 per cent. The acid added was transformed into p-aminoacetophenone which was partially used for levorin synthesis and partially accumulated in the mycelium in a free state. In this case the synthesis of levorin was limited by the metabolites forming the macrolide ring. When the precursors of the macrolide ring and the aromatic group were simultaneously added to the medium, the content of free p-aminoacetophenone in the mycelium decreased while the antibiotic activity increased by 25 per cent.

Topics: 4-Aminobenzoic Acid; Acetophenones; Aminobenzoates; Antifungal Agents; Candicidin; Free Radicals; Streptomyces

A method for spectrophotometric determination of p-aminoacetophenone (p-AAP) in the mycelium and fermentation broth filtrates of organisms producing polyenic macrolide antibiotics is described. The level of p-AAP accumulation was studied as applicable to the biosynthesis of levorin, a polyenic antibiotic of the heptaen series. The levels of p-AAP under usual conditions of the levorin-producing organism cultivation and under conditions of its stimulation with the products of the vital activity of yeast-like fungi were compared. Higher levels of p-AAP in the cultures grown with stimulation of the antibiotic biosynthesis were noted. Inadequacy of the correlation between production of levorin and p-AAP is discussed.

Topics: Acetophenones; Antifungal Agents; Candicidin; Candida; Culture Media; Free Radicals; Spectrophotometry, Ultraviolet; Streptomyces