A multistep (semi)-continuous biocatalytic setup for the production of polycaprolactone

Biocatalysis has gained increasing importance as an eco-friendly alternative for the production of bulk and fine chemicals. Within this paradigm, Baeyer Villiger monoxygenases (BVMOs) serve as enzymatic catalysts that provide a safe and sustainable route to the conventional synthesis of lactones, such as caprolactone, which is employed for the production of polycaprolactone (PCL), a biocompatible polymer for medicinal applications. In this work, we present a three-step, semi-continuous production of PCL using an entirely biocatalytic process, highlighting the merits of continuous manufacturing for enhancing biocatalysis. First, caprolactone is produced in batch from cyclohexanol using a coenzymatic cascade involving an alcohol dehydrogenase (ADH) and BVMO. Different process parameters and aeration modes were explored to optimize the cascade's productivity. Secondly, the continuous extraction of caprolactone into an organic solvent, needed for the polymerization step, was optimized. 3D-printed mixers were applied to enhance the mass transfer between the organic and the aqueous phases. Lastly, we investigated the ring-opening polymerization of caprolactone to PCL catalyzed by Candida antarctica lipase B (CAL-B), with a focus on eco-friendly solvents like cyclopentyl-methyl-ether (CPME). Space-time-yields up to 58.5 g L^-1 h^-1 were achieved with our overall setup. By optimizing the individual process steps, we present an efficient and sustainable pathway for PCL production.