Integrated High-Purity Sialic Acid Production Process Using Multi-Stage Membrane Filtration Coupled with Resin Adsorption

This study presents a novel, integrated membrane–resin hybrid platform for the high-efficiency purification of N-acetylneuraminic acid (sialic acid, NANA) from complex microbial fermentation broths. By synergistically combining four sequential stages—ceramic microfiltration (50 nm), ultrafiltration (3 kDa), nanofiltration (150 Da), and dual-resin purification (macroporous adsorption + cation-exchange)—the process achieves stepwise removal of cells, proteins, pigments, monovalent salts, and divalent metal ions without using organic solvents or high-salt buffers. Critically, each stage demonstrates high target recovery: 76.2% (CM), 67.3% (UF), and 77.5% (NF), with near-quantitative retention (>95%) during resin treatment due to NANA’s low hydrophobicity and electrostatic repulsion at pH 6.8. Following optimised acidification crystallisation (acetic acid dosage = 3 × concentrate volume; sialic acid concentrate concentration = 333.49 g/L), the final product reaches 97.9% purity with a crystalline yield of 78.6%. This scalable, green purification strategy eliminates major bottlenecks in downstream processing and enables industrial-scale production of pharmaceutical-grade sialic acid, with broad applicability to other high-value acidic biomolecules.