Phase I and phase II enzymes produced by Cunninghamella elegans for the metabolism of xenobiotics

Abstract

The filamentous fungus Cunninghamella elegans has the ability to metabolize xenobiotics, including polycyclic aromatic hydrocarbons and pharmaceutical drugs, by both phase I and II biotransformations. Cytosolic and microsomal fractions were assayed for activities of cytochrome P450 monooxygenase, aryl sulfotransferase, glutathione S-transferase, UDP-glucuronosyltransferase, UDP-glucosyltransferase, and N-acetyltransferase. The cytosolic preparations contained activities of an aryl sulfotransferase (15.0 nmol min −1 mg −1), UDP-glucosyltransferase (0.27 nmol min −1 mg −1) and glutathione 5-transferase (20.8 nmol min −1 mg −1). In contrast, the microsomal preparations contained cytochrome P450 monooxygenase activities for aromatic hydroxylation (0.15 nmol min −1 mg −1) and N-demethylation (0.17 nmol min −1~' mg −1) of cyclobenzaprine. UDP-glucuronosyltransferase activity was detected in both the cytosol (0.09 nmol min −1 mg −1) and the microsomes (0.13 nmol min −1 mg −1). N-Acetyltransferase was not detected. The results from these experiments provide enzymatic mechanism data to support earlier studies and further indicate that C. elegans has a broad physiological versatility in the metabolism of xenobiotics.