A continuous single organic phase process for the lipase catalyzed synthesis of peroxy acids increases productivity

The design of an optimal process is particularly crucial when the reactants deactivate the biocatalyst. The reaction cascades of the chemo-enzymatic epoxidation where the intermediate peroxy acid is produced by an enzyme are still limited by enzyme inhibition and deactivation by hydrogen peroxide. To avoid additional effects caused by interfaces (aq/org) and to reduce the process limiting deactivation by the substrate hydrogen peroxide, a single-phase concept was applied in a fed-batch and a continuous process (stirred tank), without the commonly applied addition of a carrier solvent. The synthesis of peroxyoctanoic acid catalyzed by Candida antarctica lipase B was chosen as the model reaction. Here, the feasibility of this biocatalytic reaction in a single-phase system was shown for the first time. The work shows the economic superiority of the continuous process compared to the fed-batch process. Employing the fed-batch process reaction rates up to 36 mmol h^-1 per gram_cat, and a maximum yield of 96 % was achieved, but activity dropped quickly. In contrast, continuous operation can maintain long-term enzyme activity. For the first time, the continuous enzymatic reaction could be performed for 55 h without any loss of activity and with a space-time yield of 154 mmol L^-1 h^-1, which is three times higher than in the fed-batch process. The higher catalytic productivity compared to the fed-batch process (34 vs. 18 g_Prod g^-1 _cat) shows the increased enzyme stability in the continuous process.