TRANSFORMATION OF THE RECALCITRANT PHARMACEUTICAL COMPOUND CARBAMAZEPINE BY THE WHITE-ROT FUNGUS PLEUROTUS OSTREATUS

Naama Golan-Rozen 1,2 Yitzhak Hadar 1 Benny Chefetz 2
1Department of Plant Pathology and Microbiology, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot
2Department of Soil and Water Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot

Carbamazepine is a widely used anticonvulsant drug. It exhibits very limited removal efficiency in municipal wastewater-treatment plants and shows high persistence in the environment. Carbamazepine can be introduced into agricultural soils via irrigation with reclaimed wastewater, and recently has been shown be taken up by crops, Thus the study of bio-degradation of carbamazepine is highly important to better remove this persistent compound from the environment.

This study aims to elucidate the metabolic pathway of carbamazepine by the white rot fungus Pleurotus ostreatus grown both in liquid medium and lingocellulosic substrate (cotton stalks). When P. ostreatus was grown in liquid medium which support both cytochrome P450 and manganese peroxidase (MnP), 99% of the added carbamazepine were transformed to 10,11- epoxycarbamazepine, and at the end of the incubation period a new metabolite, 10,11-Dihydro-10,11-dihydroxycarbamazepine was formed. When both cytochrome P450 and MnP were inactivated, only 30% of the carbamazepine were removed. Thus we suggest that these two activities are involved in the oxidation of carbamazepine in liquid culture.

When P. ostreatus was grown on cotton stalks, 90% of the added carbamazepine have been removed within ~30 days. In addition to 10,11- epoxycarbamazepine and 10,11-Dihydro-10,11-dihydroxycarbamazepine, other metabolites have also been identified. At the same conditions when 10,11-Dihydro-10,11-dihydroxycarbamazepine was the substrate, more than 90% of the added compound was removed. In contrary, when 10,11-Dihydro-10,11-dihydroxycarbamazepine was added to a fungus grown in liquid medium, it was not transformed. These results might indicate that different enzymatic mechanisms are active when the fungus is grown on cotton stalks. 








 




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