Igor A. Parshikov

Microbiological Transformation of Enrofloxacin by the Fungus Mucor ramannianus

ABSTRACT Enrofloxacin metabolism by Mucor ramannianus was investigated as a model for the biotransformation of veterinary fluoroquinolones. Cultures grown in sucrose-peptone broth were dosed with enrofloxacin. After 21 days, 22% of the enrofloxacin remained. Three metabolites were identified: enrofloxacin N-oxide (62% of the total absorbance), N-acetylciprofloxacin (8.0%), and desethylene-enrofloxacin (3.5%).

Metabolism of the veterinary fluoroquinolone sarafloxacin by the fungus Mucor ramannianus

To investigate the microbial biotransformation of veterinary fluoroquinolones, Mucor ramannianus was grown in sucrose/peptone broth with sarafloxacin for 18 days. Cultures were extracted with ethyl acetate and extracts were analyzed by liquid chromatography. The two metabolites (26% and 15% of the A280, respectively) were identified by mass and 1H nuclear magnetic resonance spectra as N-acetylsarafloxacin and desethylene-N-acetylsarafloxacin. The biological formation of desethylene-N-acetylsarafloxacin has not been previously observed. Journal of Industrial Microbiology & Biotechnology (2001) 26, 140–144.

Biotransformation of N-acetylphenothiazine by fungi

Abstract Cultures of the fungi Aspergillus niger, Cunninghamella verticillata, and Penicillium simplicissimum, grown in a sucrose/peptone medium, transformed N-acetylphenothiazine to N-acetylphenothiazine sulfoxide (from 13% to 28% of the total) and phenothiazine sulfoxide (from 5% to 27%). Phenothiazin-3-one (4%) and phenothiazine N-glucoside (4%) were also produced by C. verticillata. The probable intermediate, phenothiazine, was detected only in cultures of P. simplicissimum (6%).

Formation of conjugates from ciprofloxacin and norfloxacin in cultures of Trichoderma viride

The formation of conjugates from two antibacterial fluoroquinolone drugs, ciprofloxacin and norfloxacin, was observed in cultures of Trichoderma viride that had been grown in sucrose-peptone broth and extracted 16 d after dosing with the drugs. Both conjugates were purified by high-performance liquid chromatography and found to be optically active. They were identified by mass and proton nuclear magnetic resonance spectra as 4-hydroxy-3-oxo-4-vinylcyclopent-1-enyl ciprofloxacin and 4-hydroxy-3-oxo-4-vinylcyclopent-1-enyl norfloxacin. The transformation of veterinary fluoroquinolones in the presence of fungi may have ecological significance.

Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans

1. To determine the ability of fungi to metabolize sulphur- and oxygen-containing azaarenes, Cunninghamella elegans ATCC 9245 was grown in 125-ml flasks containing fluid Sabouraud medium. The cultures and controls were incubated at 28°C with shaking and dosed with 16.7 mM phenothiazine or phenoxazine. After incubation for 72h, the mycelia and filtrates were extracted with ethyl acetate and the combined residues analysed by high-performance liquid chromatography. Residual phenothiazine and phenoxazine were 21 and 22%, respectively, of the total UV absorbance at 254 nm. 2. The metabolites were identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. The fungus oxidized phenothiazine to phenothiazine sulphoxide, 3-hydroxyphenothiazine sulphoxide, phenothiazin-3-one, and 3-hydroxyphenothiazine and oxidized phenoxazine to phenoxazin-3-one. 3. Three of the four compounds produced by C. elegans from phenothiazine were identical to those produced by mammals, supporting the use of the fungus as a microbial model for drug metabolism.

Microbiological transformation of derivatives of 4-phenyl-2-pyrrolidone by mycelial fungi

In the microbiological transformation of 4-phenylpyrrolidine by growing strains of the fungi Cunninghamella,Beauveria, andPenicillium, its 1-ethyl and 1-acetyl derivatives are formed; these are subsequently oxidized at positions 2 and 3. In contrast, 1-benzoyl-4-phenylpyrrolidine is hydroxylated by those same cultures in positions 3 and 5. For the corresponding 2-pyrrolidone derivatives, the 4-phenyl-2-pyrrolidone is not transformed by these fungi, while the 1-benzoyl-2-pyrrolidone is hydrolyzed at the benzamide group under the same conditions. The structures of the products from these transformations were determined by mass spectrometry.