Integrated process development of a reactive extraction concept for itaconic acid and application to a real fermentation broth

Itaconic acid (IA) has a high potential to be used as a bio-based platform chemical and its biocatalytic production via fermentation has significantly improved within the last decade. Additionally downstream processing using reactive extraction (RE) was described, potentially enabling a more efficient sustainable bioprocess producing IA. The bottleneck to overcome is the connection of up- and downstream processing, caused by lack of biocompatibility of the RE systems and direct application to fermentation broth. Within this study, a biocompatible RE system for IA is defined (pH dependency, extraction mechanism) and used for direct application to a fermentation broth. By optimizing the biocatalyst, the production medium, and the extraction system in an integrated approach, it was possible to define critical parameters that enabled a tuning of the overall bioprocess. With an extraction yield of Y_IA = 0.80 ± 0.03, IA could be produced as sole carboxylic acid (b IA ,0 aq = 0.490 mol/kg^aq) using a RE system consisting of ethyl oleate as organic solvent and tri-n-octylamine as extractant (bT-C8 org = 0.6 mol/kg^org). This work is a proof of concept and demonstrates that by joint consideration of up- and downstream processing, optimized bioprocesses can be developed.