Phosphorylated polysaccharides: Applications, natural abundance, and new-to-nature structures generated by chemical and enzymatic functionalisation

Polysaccharides are foreseen as serious candidates for the future generation of polymers, as they are biosourced and biodegradable materials. Their functionalisation is an attractive way to modify their properties, thereby increasing their range of applications. Introduction of phosphate groups in polysaccharide chains for the stimulation of the immune system was first described in the nineteen seventies. Since then, the use of phosphorylated polysaccharides has been proposed in various domains, such as healthcare, water treatment, cosmetic, biomaterials, etc. These alternative usages capitalize on newly acquired physico-chemical or biological properties, leading to materials as diverse as flame-resistant agents or drug delivery systems. Phosphorylated polysaccharides are found in Nature and need to be extracted to assess their biological potential. However, they are not abundant, often present complex backbones hard to characterize, and most of them have a low phosphate content. These drawbacks have pushed forward the development of chemical phosphorylation employing a wide variety of phosphorylating agents to obtain polysaccharides with a large range of phosphate content. Chemical phosphorylation requires the use of harsh conditions and toxic, petroleum-based solvents, which hinders their exploitation in the food and health industry. Over the last 20 years, although enzymes are regiospecific catalysts that work in aqueous and mild conditions, enzymatic phosphorylation has been little investigated. To date, only three families of enzymes have been used for the in vitro phosphorylation of polysaccharides. Considering the number of unresolved metabolic pathways leading to phosphorylated polysaccharides, the huge diversity of kinase sequences, and the recent progress in protein engineering one can envision native and engineered kinases as promising tools for polysaccharide phosphorylation.