Extraction of clavulanic acid in aqueous two-phase systems followed by separation through ultrafiltration

Clavulanic acid (CA) is an important beta-lactam antibiotic that acts as an inhibitor of beta-lactamase enzymes produced by pathogenic bacteria. Tangential filtration processes such as microfiltration (MF) and ultrafiltration (UF) are used, respectively, in the removal of biomass and proteins from the fermentation broth. In the extraction step, processes with UF membranes have been studied, and extraction processes through organic solvent and aqueous two-phase systems (ATPS) have been developed. The ATPS, usually composed by polyethylene glycol (PEG) and a salt (e.g., phosphate) are used in the most of biotechnological processes. It is commonly known that ethanol is able to remove some salts in solution, such as phosphate, through precipitation. This work aims to: 1) Specify the extraction and ultrafiltration parameters of PEG/CA system, such as the partition coefficient of CA (K-p) and fouling index (I), for PEG's of different molecular weights; 2) Evaluate the ultrafiltration performance of PEG rejection (sigma(PEG)) with and without ethanol.