Enzymatic synthesis of structured DHA phospholipids in a solvent- free medium with potential effects in the treatment of neurodegenerative diseases

Abstract Phospholipids containing docosahexaenoic acid (DHA) esterified at the sn-2 position of glycerol could contribute to the prevention of neurodegenerative diseases such as Alzheimer's. Optimizing the synthesis bioprocesses for these structured DHA lipids is essential to ensure their bioavailability, allowing them to cross the blood-brain barrier and be efficiently incorporated into neuronal membranes. Lipases and phospholipases are gaining attention due to their role as biocatalysts in selectively modifying and producing structured lipids. In particular, enzymatic processes in solvent-free media are highly valued for their ecological, economic, and technological benefits. Immobilization and post-immobilization techniques are indispensable for obtaining highly stable biocatalysts in solvent-free media. The immobilized derivative of phospholipase Quara® LowP (QlowP-C18) is the optimal catalyst for synthesizing di-substituted DHA phospholipids, achieving a yield of 58%. The post-immobilization technique increases the stability of QlowP-C18 threefold, allowing it to be reused for up to five reaction cycles at 40ºC.