## 4 Discussion  
Here we demonstrated the versatility of an uncommon model (_P. oxalicum_), used in the biotransformation of four anti-inflammatory and one analgesic compound. Previously demonstrated was the capability of this fungus to degrade polycyclic aromatic compounds and diclofenac [19; 23], however, the degradation of a complex mix of drugs was unexplored in this model. There are reports of degradation in mixtures of pharmaceutical compounds with fungi. In this context, the ability of the white-rot fungi _Trametes versicolor_ was tested in the biodegradation of a mix of diclofenac, ibuprofen, naproxen and ketoprofen, with 0.03 uM as the initial concentration of each drug. It was observed that under experimental conditions a complete removal rate of 4 of these drugs was achieved in 48 h, with the exception of ketoprofen [24]. The degradation time results are consistent with those obtained in the present work. This is despite the greater level of efficiency of _P. oxalicum_, when starting from concentrations of 50 uM of each drug. The degradation efficiency of the ascomycete model _P. oxalicum_ was compared with the basidiomycetes _Bjerkandera_ sp. R1, _Bjerkandera_ _adusta_ and _Planerochaete chrysosporium_. In this case, degradation of several pharmaceutical compounds and personal care products was observed in these models. This included anti-inflammatory drugs (diclofenac, ibuprofen and naproxen), antidepressants (citalopram and fluoxetine), psychiatric drugs (diazepam), antibiotics (sulfamethoxazole), anti-epileptics (carbamazepine) and fragrances (celestolide, galaxolide and tonalide). The versatility of both systems was similar and a 100% removal rate was achieved in almost all cases [16]. It was demonstrated that fungi can degrade a variety of compounds for bioremediation purposes under different conditions. Achieving high removal rates is a challenge that occurs in the processes of bioremediation, and one that relies on the specific mechanism (intra- and/or extracellular) of each fungus. For example, the degradation observed by co-metabolic mechanisms of carbamazepine, sulfamethoxazole and sulfametizole by _Apergillus niger_ was a removal rate of 20% [25]. Figure 5: Analysis of the toxicity of effluent inoculated with NSAIDs/analgesic treated with _Penicillium oxalicum_ in a batch feed fluidised bioreactor at different incubation times. (**a**) Microtoxicity of samples taken at 0, 30, 96, 108 192 h; the control corresponds to the measurement of the microtoxicity of the medium without drugs and the fungus. (**b**) Phytotoxicity by calculation of the germination index (GI) at 48 h, the initial time point corresponds to the initial conditions of drug concentration in the bioreactor (250 uM). The final time point corresponds to a value of \(>\)99% drug degradation after 192 h of treatment. The control corresponds to the measurement of the GI using distilled water. The values are presented as the average of three independent experiments \(\pm\) standard deviation (\(n=3\)). ** = \(p<0.01\); * = \(p<0.05\). Authors suggested that the complex chemical structure might affect the removal rate. In contrast, with the use of _Trantees versicolor_ it was possible to completely degrade naproxen (31.4 uM as initial concentration) in less than six hours by a mix of intra- and extracellular processes [14]. In this work, we reported that glucose concentration affects the ability of _P. oxalicum_ to degrade a complex mix of pharmaceutical compounds. It was suggested that fungi have a co-metabolic tendency towards the elimination of xenobiotics [3]; for example, in the biodegradation of several antibiotics by _A. niger_, where the biodegradation depended on an accessible carbon source [25]. Additionally, in the biodegradation of pyrene by _Pseudotrametes gibbosa_ in the presence of co-substrates, the biodegradation efficiency of this PAH ranged from 34.23% to 50.64% [26].