An overview and future prospects of sialic acids

Sialic acids (Sias) are negatively charged functional monosaccharides present in a wide variety of natural sources (plants, animals and microorganisms). Sias play an important role in many life processes, which are widely applied in the medical and food industries as intestinal antibacterials, antivirals, anti-oxidative agents, food ingredients, and detoxification agents. Most Sias are composed of N-acetylneuraminic acid (Neu5Ac, >99%), and Sia is its most commonly used name. In this article, we review Sias in terms of their structures, applications, determination methods, metabolism, and production strategies. In particular, we summarise and compare different production strategies, including extraction from natural sources, chemical synthesis, polymer decomposition, enzymatic synthesis, whole-cell catalysis, and de novo biosynthesis via microorganism fermentation. We also discuss research on their physiological functions and applications, barriers to efficient production, and strategies for overcoming these challenges. We focus on efficient de novo biosynthesis strategies for Neu5Ac via microbial fermentation using novel synthetic biology tools and methods that may be applied in future. This work provides a comprehensive overview of recent advances on Sias, and addresses future challenges regarding their functions, applications, and production.