Evaluation of diclofenac biodegradation by the ascomycete fungus Penicillium oxalicum at flask and bench bioreactor scales.

Diclofenac (DFC) is a common anti-inflammatory drug, and has attracted the significant attention due to its massive use around the world and its environmental impact. In this work, we describe for the first time the use of Penicillium oxalicum, an ascomycetes fungus, for the biotransformation of DFC at flask and bench bioreactor scales. We present a complete study of the role of enzymes, metabolic pathway, acute toxicity assays and comparison between free and immobilised biomass. Pellets of P. oxalicum degraded 100 µM of DFC within 24 h, and the activity of CYP450 enzymes was key for the elimination of the drug. The scaling-up to bench bioreactor was optimised by the reduction of nutrients, and characterising the actions of free pellets, polyurethane foam- and plastic K1-immobilised biomass revealed free pellets to be the most efficient DFC removal system (total elimination occurred in 36 h). Hydroxylated metabolites were detected during the process, suggesting that a mixture of biological and physical processes were involved in the elimination of DFC. The use of P. oxalicum reduced the acute toxicity of the medium supplemented with diclofenac and represents a novel and attractive alternative for the elimination of pharmaceutical compounds.