Novel metabolites from Cunninghamella elegans as a microbial model of the β-blocker carvedilol biotransformation in the environment

Abstract

Beta-adrenergic blocking agents like carvedilol are widely detected environmental pollutants. Its human metabolism is well known, while the fate of the carvedilol when metabolized by environmental strains is unknown. The aim of this study was to investigate the mechanism and pathways of carvedilol metabolism by the common environmental fungal strain Cunninghamella elegans. In this report the process of carvedilol biotransformation by C. elegans was described for the first time. A total of ten carvedilol derivatives were identified in C. elegans cultures. Similarly to mammalian metabolism of carvedilol, its fungal biotransformation proceeded through hydroxylation and conjugation reactions. However, in C. elegans cultures new products such as methyl-phenyl carvedilol and glucose-desmethyl carvedilol were identified, which had not been previously detected in human and animals. Moreover, an involvement of cytochrome P450 and cytochrome P450 reductase in carvedilol fungal metabolism was revealed.