Abstract
The valorization of cheese whey, a rich by-product of the dairy industry that is rich in lactose (approx. 70%), proteins (14%), and minerals (9%), represents a promising approach for microbial fermentation. With global whey production exceeding 200 million tons annually, the high biochemical oxygen demand underlines the important need for sustainable processing alternatives. This review explores the biotechnological potential of whey as a fermentation medium by examining its chemical composition, microbial interactions, and ability to support the synthesis of valuable metabolites. Functional microorganisms such as lactic acid bacteria (Lactobacillus helveticus, L. acidophilus), yeasts (Kluyveromyces marxianus), actinobacteria, and filamentous fungi (Aspergillus oryzae) have demonstrated the ability to efficiently convert whey into a wide range of bioactive compounds, including organic acids, exopolysaccharides (EPSs), bacteriocins, enzymes, and peptides. To enhance microbial growth and metabolite production, whey fermentation can be carried out using various techniques, including batch, fed-batch, continuous and immobilized cell fermentation, and membrane bioreactors. These bioprocessing methods improve substrate utilization and metabolite yields, contributing to the efficient utilization of whey. These bioactive compounds have diverse applications in food, pharmaceuticals, agriculture, and biofuels and strengthen the role of whey as a sustainable biotechnological resource. Patents and clinical studies confirm the diverse bioactivities of whey-derived metabolites and their industrial potential. Whey peptides provide antihypertensive, antioxidant, immunomodulatory, and antimicrobial benefits, while bacteriocins and EPSs act as natural preservatives in foods and pharmaceuticals. Also, organic acids such as lactic acid and propionic acid act as biopreservatives that improve food safety and provide health-promoting formulations. These results emphasize whey's significant industrial relevance as a sustainable, cost-efficient substrate for the production of high-quality bioactive compounds in the food, pharmaceutical, agricultural, and bioenergy sectors.