Sustainable bioprocessing strategies for scalable <scp>d</scp> -tagatose production: From enzyme engineering to industrial implementation

Carbohydrates are essential nutrients that serve as primary energy sources and structural components in living organisms. However, excessive consumption of conventional sugars has been increasingly linked to global health burdens such as obesity, diabetes, and metabolic disorders, as well as environmental concerns including greenhouse gas emissions. d-Tagatose, a naturally occurring rare sugar, has attracted considerable attention due to its low caloric value, prebiotic effects, and anti-obesity and anti-diabetic properties. Recent breakthroughs in targeted chemo-enzymatic synthesis, combined with directed evolution and systems metabolic engineering, have enabled more efficient and scalable production routes. Concurrently, the valorization of agricultural and food processing wastes as alternative raw materials aligns with circular bioeconomy principles and enhances sustainability. This review provides a comprehensive overview of recent technical advances, benefits, and ongoing challenges in d-tagatose production. We also highlight emerging strategies to facilitate commercialization and position d-tagatose as a cornerstone of the next generation of health-promoting sweeteners.