Aspergillus niger prolyl endopeptidase (An-PEP)

Aspergillus niger prolyl endopeptidase (An-PEP) is an acid-stable serine protease derived from the filamentous fungus Aspergillus niger. It is uniquely characterized by its ability to efficiently cleave proline-rich peptides, such as gluten, at the carboxyl side of internal proline residues, even in the highly acidic environment of the human stomach (pH 2.0–5.0) [1, 13, 14]. This biological function makes it a significant therapeutic agent for managing gluten-related disorders, including celiac disease and non-celiac gluten sensitivity. In these conditions, the ingestion of gluten leads to the formation of immunogenic peptides that trigger inflammatory responses in the small intestine; An-PEP acts by degrading these peptides into smaller, non-toxic fragments before they reach the intestinal mucosa [1, 18]. Beyond its use as a digestive aid (e.g., Tolerase G), proteins from Aspergillus niger, such as alpha-galactosidase and glucose oxidase, are widely used in industrial biotechnology and diagnostics [11, 19]. In the context of drug discovery, the term "Aspergillus niger protein" is often used generically in computational docking studies to refer to specific fungal enzymes like Esterase A (EstA) or to the broader proteome as a target for antifungal agents [4, 10, 11]. While these proteins serve as important tools and therapeutic agents, the name is non-specific and can refer to any member of the fungal proteome, including those targeted by antifungal drugs like azoles (which target lanosterol 14-alpha demethylase) and echinocandins (which target beta-glucan synthase) [2, 17].

Other names

Prolyl endoproteaseProlyl oligopeptidaseAn-PEPTolerase GAspergillus niger protein (generic)Aspergillus niger prolyl endoproteaseAspergillus niger acid proteaseEsterase A (EstA)Alpha-galactosidase

Aspergillus niger prolyl endopeptidase (An-PEP) functions as an exogenous digestive enzyme that cleaves proline-rich gluten peptides at the carboxyl side of internal proline residues in the stomach. This enzymatic degradation neutralizes the immunogenic potential of gluten fragments before they can reach the small intestine and trigger an autoimmune or inflammatory response in sensitive individuals [1, 14, 18].