Whey, a by‐product of the cheese manufacturing industry, represents one of the most abundant and polluting effluents in the global food industry. Despite traditionally being underutilized and often discarded, its rich nutrient profile, particularly protein and lactose, has increasingly sparked an interest in its value within biotechnological processes. This review analyses the potential of whey as a sustainable substrate for the microbial production of value‐added bioproducts, focussing on L‐threonine production as a strategic case study, while addressing the environmental impact of inadequate disposal and current utilization strategies. A comparative analysis with other agroindustrial waste demonstrates whey’s competitive advantages in terms of composition, cost‐effectiveness and sustainability metrics. Furthermore, L‐threonine biological and industrial importance, and the most relevant advances in metabolic engineering, optimized fermentation and emerging tools such as optogenetics and machine learning are discussed, as they facilitate enhanced L‐threonine yields through the creation of robust, high‐producing strains. Technoeconomic analysis at pilot scale (33.8 tons/year) indicates that whey‐based production offers a comparative cost advantage of 7.4% over glucose‐based processes (20.55 USD/kg vs. 22.20 USD/kg). While absolute costs at pilot scale exceed current industrial market prices (1.31–1.66 USD/kg)—reflecting typical scale effects—the demonstrated comparative advantage and substantial environmental benefits (waste valorization, elimination of disposal costs and circular economy alignment) position whey‐based L‐threonine production as a strategic biorefinery opportunity with significant potential for industrial‐scale implementation. This cost benefit is primarily driven by the lower market price of whey compared to commercial glucose substrates, which compensates for the slightly higher downstream processing costs (5.90 vs. 5.40 USD/kg) required for complex matrices. Downstream processing considerations, including recovery, purity requirements and economic viability, are comprehensively addressed. This review concludes that whey, far from being merely a pollutant, has the characteristics required to become an asset for biotechnology. Utilizing whey as a culture medium for L‐threonine production by E. coli in bioreactors not only offers a solution to mitigate a significant environmental issue but also opens a path for the cost‐effective, sustainable production of a globally high‐demand amino acid. Whey represents a strategic biorefinery platform with potential for industrial‐scale implementation. Continued research and development in this area are fundamental to fully realizing this potential.
Vélez et al. (Thu,) studied this question.