Overview on the Biochemical Potential of Filamentous Fungi to Degrade Pharmaceutical Compounds

Abstract

Pharmaceuticals represent an immense business with increased demand due to intensive livestock raising and an aging human population, which guarantee the quality of human life and well-being. However, the development of removal technologies for these compounds is not keeping pace with the swift increase in their use. Pharmaceuticals constitute a potential risk group of multiclass chemicals of increasing concern since they are extremely frequent in all environments and have started to exhibit negative effects on micro- and macro-fauna as well as on human health. In this context, fungi are known to be extremely diverse and poorly studied microorganisms despite being well suited for bioremediation processes, taking into account their metabolic and physiological characteristics for the transformation of even highly toxic xenobiotic compounds. Increasing studies indicate that fungi can transform many structures of pharmaceutical compounds, including anti-inflammatories, β-blockers, and antibiotics. This is possible due to different mechanisms in combination with the extracellular and intracellular enzymes, which have broad of biotechnological applications. Thus, fungi and their enzymes could represent a promising tool to deal with this environmental problem. Here, we review the studies performed on pharmaceutical compounds biodegradation by the great diversity of these eukaryotes. We examine the state of the art of the current application of the Basidiomycota division, best known in this field, as well as the assembly of novel biodegradation pathways within the Ascomycota division and the Mucoromycotina subdivision from the standpoint of shared enzymatic systems, particularly for the cytochrome P450 superfamily of enzymes, which appear to be the key enzymes in these catabolic processes. Finally, we discuss the latest advances in the field of genetic engineering for their further application.

Metabolic Capability of Penicillium oxalicum to Transform High Concentrations of Anti-Inflammatory and Analgesic Drugs

“…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].…”

“…In general, fungi can use two systems to degrade pharmaceutical compounds; the first is the system related to lignin-modifying (LME) extracellular enzymes (mainly associated with basidiomycetes), and secondly, the detoxification system mediated by CYP450 enzymes. The latter were responsible for the elimination of xenobiotics in fungi lacking an extracellular ligninolytic system [3]. Some aspergilla can remove pharmaceutical compounds under saline conditions [27], and are mediated by LME (esterases, laccases and peroxidases).…”

“…It was reported that the main intracellular pathway for the metabolism of drugs in fungi is by the action of CYP450 enzymes. They are a large group of enzymes that are related to many cellular processes, where certain clans have been associated in the degradation of aromatics compounds by hydroxylation of the main ring [3]. In this work, the presence of various mono-, and di-hydroxylated compounds was evidenced (i.e., 3-hydroxy-acetaminophen; 4, 5-dihydroxy-diclofenac; 2-[3-(3,4-dihydroxybenzoyl) phenyl]-propanoic acid) as the result of the CYP450 enzymes action.…”

“…The morphological and enzymatic capabilities of these organisms allow them to degrade and/or remove large numbers and types of compounds (including xenobiotic substances) using both enzymatic and biophysical processes such as bioaccumulation and biosorption. For this reason, they are promising models to implement new eco-friendly technologies [2,3].…”

Isolation of Fungal Strains from Municipal Wastewater for the Removal of Pharmaceutical Substances

“…They are able to degrade a wide variety of pharmaceuticals due to their enzymatic processes. Furthermore, fungi can use a biosorption strategy to counteract the effects of pharmaceuticals because of their specific cell wall composition, formed from chitosan and chitin [8,9]. In addition, Trametes versicolor can metabolize and integrate some pharmaceuticals, such as benzophenone-3 and diclofenac, into amino acids of fungi [10,11].…”