Background: Amiodarone represents a principal antiarrhythmic pharmaceutical drug available in the market for the treatment of ventricular arrhythmias. However, despite its better efficacy, the usage of amiodarone is associated with extracardiac toxicity. The human body evolved a system of cytochrome P450 enzymes which play an essential role in the metabolism of harmful foreign substances. Therefore, CYP enzymes may either lead to the elimination or degradation of the leftover drug residues.

Objective: The present study focused on successful utilization of Saccharomyces cerevisiae strain OBS2 with probiotic- cum- therapeutic potential and expressing in silico enhanced human cytochrome P4503A4 for the degradation of leftover drug residues of amiodarone in vitro and in vivo.

Methodology: In this study, cytochrome P4503A4 (1W0E) was taken as a template and the predicted 3D model of mutant CYP3A4 was developed using different bioinformatics tools. Selected mutant (Glu165Asp) protein was reverse translated and transcribed into cDNA sequence. The cDNA of CYP3A4 was synthesized, cloned into p427TEF construct and transformed into Saccharomyces cerevisiae OBS2. The degradation of leftover drug residues of amiodarone in vitro and in vivo using recombinant Saccharomyces cerevisiae OBS2 expressing CYP3A4 was evaluated.

Result: The CYP3A4 activity in recombinant probiotic yeast was observed as 108 IU/mL and in vitro degradation of leftover drug residues of amiodarone was observed as 66.32 %. Whereas, in vivo degradation of leftover drug residues of amiodarone was observed as 72.61 % along with recovery of organ damage in histopathological studies of the animal model.

Conclusion: Saccharomyces cerevisiae OBS2 expressing CYP3A4 can be used for probiotic and therapeutic applications.

• PMID: 32305697
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Journal Article

Authors

Banoth S, Tangutur AD, Anthappagudem A, Ramaiah J, Bhukya B

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