Biotransformation of progesterone by endophytic fungal cells immobilized on electrospun nanofibrous membrane.

Biotransformation of steroids by fungi has been raised as a successful, eco-friendly, and cost-effective biotechnological alternative for chemical derivatization. Endophytic fungi live inside vegetal tissues without causing damage to the host plant, making available unique enzymes that carry out uncommon reactions. Moreover, using nanofibrous membranes as support for immobilizing fungal cells is a powerful strategy to improve their performance by enabling the combined action of adsorption and transformation processes, along with increasing the stability of the fungal cell. In the present study, we report the use of polyacrylonitrile nanofibrous membrane (PAN NFM) produced by electrospinning as supporting material for immobilizing the endophytic fungus Penicillium citrinum H7 aiming the biotransformation of progesterone. The PAN@H7 NFM displayed a high progesterone transformation efficiency (above 90%). The investigation of the biotransformation pathway of progesterone allowed the putative structural characterization of its main fungal metabolite by GC-MS analysis. The oxidative potential of P. citrinum H7 was selective for the C-17 position of the steroidal nucleus.

Biotransformation of hydroxychloroquine to evaluate the cytotoxicity of its metabolites and mimic mammalian metabolism.

Hydroxychloroquine (HCQ) displays attractive anti-inflammatory and antiviral effects. Because of that, such a drug made part of some clinical trials for combating Sars-CoV-2 during the COVID-19 pandemic. The present study aimed to conduct the biotransformation of HCQ by filamentous fungi reported as microbial models of mammalian drug metabolism to evaluate its cytotoxic after metabolization. Cunninghamella echinulata var. elegans ATCC 8688a could efficiently biotransform HCQ into one main metabolite identified as the new 4-(1,2,3,4-tetrahydroquinolin-4-ylamino)pentan-1-ol (HCQ-M). The microbial transformation occurred through N-dealkylation, 7-chloro-elimination, and reduction of the two conjugated double-bond from the quinoline system of HCQ. The cytotoxic profiles of HCQ and its metabolite were evaluated using CCD-1059Sk cells (human fibroblasts) through sulforhodamine B, trypan blue, and Live/Dead assays. Both HCQ and HCQ-M displayed cytotoxic activities in human fibroblasts, but HCQ-M was significantly more toxic than HCQ. The reported findings should be considered for further clinical studies of HCQ and will be important for guidance in achieving new derivatives from it.