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Ultraviolet and Light Absorption Spectrometry
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Zoltan M. Dinya, Ferenc J. Sztaricskai
The well-known instability and occassional difficulties in the purification of the polyene macrolide antibiotics account for great care during their spectrophotometric assay. These difficulties are further enhanced because the producing microorganisms biosynthesize a mixture of antibiotic variants. Sometimes samples previously believed to be homogeneous have been found to be impure and contaiminated by additional variants. For example, nystatin [fungicidin (89)], widely used in therapy throughout the world, has been shown to be a mixture of the A1 and A2 variants after years of application [252,253]. Additionally, in certain fermentation broths several antibiotics with essentially different structure may be present. This is demonstrated by the example of the strain Streptomyces rimosus, producing—in addition to oxytetracycline (OTC; terramycin)—the glycoside antibiotic [254] rimocidin with tetraene macrolide structure [255,256] (λmax, 279, 291, 304, and 318 nm).
Paromomycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Rusheng Chew, James S. McCarthy
Paromomycin sulfate consists of a mixture of sulfate salts produced by the growth of strains of Streptomyces rimosus var. paromomycinus. As the amounts of sulfate in the end product vary by up to 10% or more, the label of paromomycin injection currently marketed expresses potency in terms of paromomycin base; 15 mg of paromomycin sulfate per kilogram is equivalent to 11 mg of paromomycin base per kilogram.
Combination of oxytetracycline and quinocetone synergistically induces hepatotoxicity via generation of reactive oxygen species and activation of mitochondrial pathway
Published in Toxicology Mechanisms and Methods, 2022
Lirui Hou, Fang Liu, Chong Zhao, Lihong Fan, Hongbo Hu, Shutao Yin
Oxytetracycline (OTC) is a linear, tetracyclic broad-spectrum antibiotic originally isolated from Streptomyces rimosus (Petkovic et al. 2006). OTC can inhibit the growth of the peptide chain, thereby affecting the protein synthesis of bacteria or other pathogenic microorganisms (Zou et al. 2018). It is widely used in livestock, aquaculture and poultry worldwide (Boonsaner and Hawker 2015; Kimera et al. 2015), and it is also one of the main antibiotics present in the environment. However, the accumulation of OTC, which has been described in chicken edible tissues, slaughtered animals and rice (Landers et al. 2012; Bao et al. 2019), can lead to toxic effects, including induce hepatotoxicity, human lymphocyte challenges, and lipid peroxidation (Jayanthi and Subash 2010; Abdel-Daim and Ghazy 2015; Di Cerbo et al. 2016).
Microbial biotransformation – an important tool for the study of drug metabolism
Published in Xenobiotica, 2019
Rhys Salter, Douglas C. Beshore, Steven L. Colletti, Liam Evans, Yong Gong, Roy Helmy, Yong Liu, Cheri M. Maciolek, Gary Martin, Natasa Pajkovic, Richard Phipps, James Small, Jonathan Steele, Ronald de Vries, Headley Williams, Iain J. Martin
The following strains are referred to in the Results section in terms of their ability to produce the targeted metabolites: SP7001 (Amycolatopsis sp.), SP7015 (Ascomycete fungus) SP7043 (Amycolatopsis lurida), SP7045 (Streptomyces sp.), SP7049 (Streptomyces rimosus), SP7050 (Streptomyces peucetius), SP7059 (Streptomyces sp.), SP7074 (Cunninghamella elegans). Compounds (6a) and (8a) underwent production-scale biotransformation to produce metabolites for purification that had been positively matched by LC-MS/MS comparison of screen-scale samples with a chemically synthesized standard (6b) or a biological reference sample (8b). Where multiple strains were deemed capable of producing a target metabolite, strain selection was made according to the yield of conversion to the target metabolite, as well as an assessment of the complexity of metabolite purification, e.g. taking the presence of any co-eluting endogenous products or non-target co-produced metabolites into consideration. Additionally, a pre-scaling confirmation step was performed to check reproduction of screening-scale results in shake-flasks, with the inclusion of a 48 h seed culture stage. Scaled-up reproduction was achieved by performing the biotransformation reactions in a sufficient number of 250 mL Erlenmeyer flasks containing 50 mL working volumes, inoculated from seed cultures prepared as used in the confirmation step. The simplicity of this approach is designed to negate potential transfer issues, a well-known liability associated with transferring processes from shaken flasks to stirred tank bioreactors. The required volume for the scaled-up biotransformation was estimated based on an approximation of the yield of conversion from the confirmation step. In the cases reported herein, the scale-up reactions were repeated at two and 6 L volumes to provide sufficient material from which a range of 5–50 mg of target metabolites at >90% purity could be obtained using the processing methods described below. Metabolite (7b) was purified directly from screening-derived materials.