Abstract

Obesity and its metabolic complications are a growing global health burden, pushing the search for safer, more effective treatments. This review looks at fungalderived therapeutic enzymes and endophytic fungi as sustainable resources for new treatments, particularly pancreatic lipase inhibitors for metabolic disease. It covers the pharmaceutical relevance of fungi like Aspergillus niger, A. oryzae, A. flavus, and Saccharomyces cerevisiae, which produce enzymes used in oncology, metabolic and digestive disorders, inflammation, thrombosis, and enzyme replacement therapy. Particular attention goes to pancreatic lipase inhibitors and fungal bioactive metabolites as anti-obesity agents that reduce dietary fat absorption with fewer side effects than current synthetic drugs. The review also examines how fungal secondary metabolites are biosynthesized and regulated, including biosynthetic gene clusters, metabolic engineering, heterologous expression, and protein engineering used to boost enzyme production and stability. Enzymes like L-asparaginase, uricase, lactase, lipase, β-glucosidase,superoxide dismutase, cytosine deaminase, and fibrinolytic enzymes are discussed by mechanism, application, and clinical status. Manufacturing topics fermentation, downstream processing, GMP, immunogenicity, and regulation round out the picture. Despite ongoing challenges in stability and scale-up, advances in synthetic biology and precision fermentation continue to position fungal biotechnology as a sustainable platform for treating obesity, cancer, and other chronic diseases.

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