The Separative Bioreactor: A Continuous Separation Process for the Simultaneous Production and Direct Capture of Organic Acids

The replacement of petrochemicals with biobased chemicals requires efficient bioprocesses, biocatalysis, and product recovery. Biocatalysis (e.g., enzyme conversion and fermentation) offers an attractive alternative to chemical processing because biocatalysis utilize renewable feedstocks under benign reaction conditions. One class of chemical products that could be produced in large volumes by biocatalysis is organic acids. However, biocatalytic reactions to produce organic acids typically result in only dilute concentrations of the product because of product inhibition and acidification that drives the reaction pH outside of the optimal range for the biocatalyst. Buffering or neutralization results in formation of the acid salt rather than the acid, which requires further processing to recover the free acid product. To address these barriers to biocatalytic organic acid production, we developed the "separative bioreactor" based on resin wafer electrodeionization, which is an electro-deionization platform that uses resin wafers fabricated from ion exchange resins. The separative bioreactor simultaneously separates the organic acid from the biocatalyst as it is produced, thus it avoids product inhibition enhancing reaction rates. In addition, the separative bioreactor recovers the product in its acid form to avoid neutralization. The instantaneous separation of acid upon formation in the separative bioreactor is one of the first truly one-step systems for producing organic acids. The separative bioreactor was demonstrated with two systems. In the first demonstration, the enzyme glucose fructose oxidoreductase (GFOR) was immobilized in the reactor and later regenerated in situ. GFOR produced gluconic acid (in its acid form) continuously for 7 days with production rates up to 1000 mg/L/hr at >99% product recovery and GFOR reactivity >30mg gluconic acid/mg GFOR/hour. In the second demonstration, the E. coli strain CSM1 produced lactic acid for up to 24 hours with a productivity of >200 mg/L/hr and almost 100% product recovery.