Microbial synthesis of mammalian metabolites of spironolactone by thermophilic fungus Thermomyces lanuginosus
Autor: | V Koteshwar Rao, S Girisham, G ShyamPrasad, B Sreelatha |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Clinical Biochemistry Fungus Spironolactone 030226 pharmacology & pharmacy Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Biotransformation medicine Canrenone Molecular Biology Pharmacology biology Chemistry Thermophile Organic Chemistry Eurotiales biology.organism_classification Transformation (genetics) 030104 developmental biology Fermentation Drug metabolism Mesophile medicine.drug |
Zdroj: | Steroids. 136:1-7 |
ISSN: | 0039-128X |
DOI: | 10.1016/j.steroids.2018.05.011 |
Popis: | Mesophilic fungi are well recognized as models of mammalian drug metabolism. Thermophilic fungi remained unexplored despite having a unique mechanism of growing at higher temperatures and performing wide diverse reactions. The present investigation is directed to isolate a promising thermophilic fungal strain capable of biotransformation using spironolactone as a model drug. Two-stage fermentation protocol was followed for the process. The transformation of spironolactone was identified by HPLC and structure elucidation of the metabolites was done with the help of LC-MS/MS analysis and previous reports. A strain of Thermomyces lanuginosus isolated from decomposed banana peel waste was found to be most promising in transforming spironolactone to 4 metabolites viz.7α-thiospironolactone (M1) canrenone (M2), 7α-thiomethylspironolactone (M3) and 6β-OH-7α-thiomethylspironolactone (M4), the major mammalian metabolites reported previously. The synthesis of metabolites of spironolactone by T. lanuginosus similar to mammals clearly states that this fungus possess enzyme system similar to mammals. Hence, this fungus has the potential to use as a model organism for studying drug metabolism. |
Databáze: | OpenAIRE |
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