Fungal Proteases as Emerging Biocatalysts to Meet the Current Challenges and Recent Developments in Biomedical Therapies: An Updated Review

Abstract

With the increasing world population, demand for industrialization has also increased to fulfill humans’ living standards. Fungi are considered a source of essential constituents to produce the biocatalytic enzymes, including amylases, proteases, lipases, and cellulases that contain broad-spectrum industrial and emerging applications. The present review discussed the origin, nature, mechanism of action, emerging aspects of genetic engineering for designing novel proteases, genome editing of fungal strains through CRISPR technology, present challenges and future recommendations of fungal proteases. The emerging evidence revealed that fungal proteases show a protective role to many environmental exposures and discovered that an imbalance of protease inhibitors and proteases in the epithelial barriers leads to the protection of chronic eosinophilic airway inflammation. Moreover, mitoproteases recently were found to execute intense proteolytic processes that are crucial for mitochondrial integrity and homeostasis function, including mitochondrial biogenesis, protein synthesis, and apoptosis. The emerging evidence revealed that CRISPR/Cas9 technology had been successfully developed in various filamentous fungi and higher fungi for editing of specific genes. In addition to medical importance, fungal proteases are extensively used in different industries such as foods to prepare butter, fruits, juices, and cheese, and to increase their shelf life. It is concluded that hydrolysis of proteins in industries is one of the most significant applications of fungal enzymes that led to massive usage of proteomics.

Cultivation conditions and biochemical characterization of the proteolytic enzymes with fibrinolytic action obtained from mushrooms in the last ten years

“…The protein catalytic reaction is formed by proteolytically converting soluble fibrinogen molecules into fibrin (polymeric) monomers that spontaneously polymerize and create a fibrin gel network, as illustrated in Figure 3 (Anna et al, 2017;Buba, 2018). The enzyme families are determined by the mechanism of action and the presence of amino acid residues (Figure 4B) to form an acyl-enzyme intermediate that covalently binds to the N-terminus of the enzyme substrate (Erez et al, 2009;Shafee, 2014;Naeem et al, 2022). Source: Erez et al, (2009).…”

Heterologous Expression of Extracellular Proteinase pAsPs of Aspergillus pseudotamarii in Komagataella phaffii

“…Secreted fungal proteases are among the major enzymes in industry, including the pharmaceutical, detergent, and leather industries [ 1 ], as well as bioactive peptides and waste-processing–related manufacturing [ 2 ]. The global market for manufacturing associated enzymes in 2011 was estimated to be approximately $3.3 billion, but in 2020 in the US alone, it was shown to be $1.5 billion and predicted to continue growing at 7.1% per year until 2027 [ 3 ].…”

“…The global market for manufacturing associated enzymes in 2011 was estimated to be approximately $3.3 billion, but in 2020 in the US alone, it was shown to be $1.5 billion and predicted to continue growing at 7.1% per year until 2027 [ 3 ]. Meanwhile, fungal proteases account for 20% to 60% of the proportion of the total enzyme market [ 2 ]. Currently, such enzymes can be obtained either by their production directly in host organisms [ 4 ] or via heterologous expression in other organisms [ 5 ].…”

“…Neutral proteases have high specificity for hydrophobic amino acid residues [ 7 ]. Enzymatic activity of fungal proteases is mediated by the formation of an intermediate acyl enzyme, which covalently attaches to the N terminus of a substrate, which is then hydrolyzed by a water molecule [ 2 ].…”

Síntese de proteases por uma espécie de fungo filamentoso anamórfico para aplicação em processo industrial

“…Muitas enzimas produzidas por cepas fúngicas já foram isoladas, todavia ainda há uma diversidade de espécies que permanecem inexplorada (Naeem et al, 2022). Com base na importância do uso fungos como fonte de enzimas, este estudo avaliou a produção de proteases por Aspergillus flavus para investigação das características para posterior aplicação industrial.…”