The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans

Abstract

The fungus Cunninghamella elegans is recognised as a microbial model of mammalian drug metabolism owing to its ability to catabolise xenobiotic compounds in an analogous fashion to animals. Its ability to produce phase I (oxidative) metabolites of drugs is associated with cytochrome P450 (CYP) activity; however, almost nothing is known about these enzymes in the fungus. In this paper we report the in silico analysis of the genome sequence of C . elegans B9769, which contains 32 genes putatively coding for CYPs. Based on their predicted amino acid sequences these were classified as belonging to CYP509, 5203, 5208, 5313, 5210, 61 and 51 families. Reverse transcription-quantitative PCR revealed that the gene coding for CYP5313D1 was significantly upregulated when C . elegans DSM1908 was cultivated in sabouraud dextrose in contrast to its expression in cells grown in Roswell Park Memorial Institute medium. This corresponded to the fungus’ xenobiotic biotransformation ability when grown in the two media. Heterologous expression of cyp5313D1 in Pichia pastoris resulted in a recombinant strain that biotransformed flurbiprofen to 4′-hydroxyflurbiprofen, the same metabolite generated by C . elegans cultures. This is the first report of a xenobiotic-biotransforming CYP from this biotechnologically important fungus.

Evaluation of the chemical constituents and potential biological activities of Cunninghamella blakesleeana

“…The present investigation shows that significant variation in the contents which previously reported to have antioxidant activities. Its ability to produce phase I (oxidative) metabolites of drugs is associated with cytochrome P450 (CYP) activity which indicate the value of using this fungi as excellent media biotransformation ( Palmer-Brown et al, 2019 ).…”

“…Members of this genus possess cytochrome P -450 monooxygenase systems analogous to those in mammals ( Chen et al, 2014 ) therefor they are used in wide range of drugs in manners similar to mammalian enzyme systems ( Kelly and Kelly, 2013 ). Accordingly this genus was used as biotransformation media due to its ability to convert molecules to valuable medicinally active substances ( Palmer-Brown et al, 2019 ).…”

The Callus of Phaseolus coccineus and Glycine max Biotransform Flavanones into the Corresponding Flavones

“…Microorganisms such as the filamentous fungi of the genus Cunninghamella can serve as models for the mammalian metabolism of xenobiotics [47], including flavonoids [48]. Primarily due to the similarities in the structure and functioning of the cytochrome P450 enzymes of microorganisms and mammals [49][50][51]. Microorganisms of the genus Cunninghamella can be used in the pharmaceutical industry in early ADME-Tox assays [52].…”

Bioactive metabolites of Cunninghamella, Biodiversity to Biotechnology

“…Thus, they have been applied to many drugs where they act in a manner that similar to those of mammalian enzyme systems [34]. For this reason, Cunninghamella species have been applied as biotransformation media, because of its capacity to convert different molecules to valuable medicinal substances [35].…”