Penicillium brefeldianum B. O. Dodge, 1933: insights into its secondary metabolites, pharmacologically active compounds and biotechnological potential

Penicillium brefeldianum is a filamentous fungus known for its ability to produce a wide range of bioactive secondary metabolites and industrially relevant enzymes. Despite its significance, no comprehensive review has yet consolidated the chemical diversity and biotechnological potential of this species. This review aimed to critically evaluate the secondary metabolites and enzymatic capabilities of P. brefeldianum, highlighting its pharmaceutical and industrial relevance. Literature review was conducted by covering studies published from 1963 to 2024. Data were compiled from peer-reviewed journals, focusing on the identification, classification, and biological activities of secondary metabolites, along with reports on enzyme production by P. brefeldianum. A total of 90 secondary metabolites were documented, including indole diketopiperazines and indole diterpenoids, as well as macrolide lactones, macrolide lactams, pyrones, chromones, statins, cyclopentenones, orcinols, pteridines and steroids. These compounds exhibit a broad spectrum of pharmacological properties, including anticancer, antimicrobial, antiviral, anti-oxidant, antidiabetic, and anti-inflammatory activities. Additionally, the fungus produces several industrially important enzymes, such as β-glucanases, xylanase, amylase, pectinase, sucrase, raffinase, and melezitase, demonstrating its utility in biotechnological applications. This review offers the first comprehensive compilation of the secondary metabolites and enzymatic profile of P. brefeldianum, underscoring its untapped potential in pharmaceutical application. It identifies future research directions, including the need for genetic and metabolic engineering approaches to optimize metabolite and enzyme production.