Abstract

Combining (photo)Biocatalysis with Continuous Flow: Efficient Biotransformations in 3D Printed Reactors

Heidrun Gruber-Wölfler, Associate Professor, Graz University of Technology

Biocatalysis has gained a lot of popularity in recent years as an eco-friendly alternative to conventional catalysis in synthetic chemistry. Enzymes have a variety of advantages, including as low toxicity, little environmental effect, high activity in moderate settings, and good selectivity. Nevertheless, new and innovative approaches are still required in order to increase the stability of biocatalysts and make biocatalytic processes in continuous flow commercially feasible. In this contribution the design of continuous, inexpensive, and stable biocatalytic processes for a more sustainable synthesis of fine chemicals will be discussed. In the first part, the design of a continuous automated process to evaluate the efficiency of the model enzyme PAD (phenolic acid decarboxylase) covalently immobilized on 3D printed supports [1] will be presented. For a Design of Experiments (DoE) evaluation, an automated control setup was operated by a Python-based application in order to quickly identify the optimal operating conditions and increase the level of process understanding.

The second part of the presentation will cover the construction and optimization of photo-bioreactors for carrying out light-driven biotransformations in recombinant cyanobacteria [2]. In particular, the stereoselective reduction of 2-methyl maleimide was investigated via a design-of-experiments approach.

Lastly, the combination of photo- and biocatalysis will be presented for a multistep flow process including an a-CF3-substituted ketone production in a self-made photoreactor, followed by an enzymatic ketoreduction catalyzed by an ADH-Lica (alcohol dehydrogenase) enzyme to obtain chiral trifluoromethylated alcohols.

Overall, our approaches successfully bridge well-established technologies in chemical engineering (such as additive manufacturing, process automation and optimization) with biotechnology (e.g. enzyme immobilization) and continuous flow to design more sustainable synthetic routes for fine chemicals and APIs.
 
[1] A. Valotta, M. C. Maier, S. Soritz, M. Pauritsch, M. Koenig, D. Brouczek, M. Schwentenwein, H. Gruber-Woelfler, J Flow Chem 2021, 11, 675–689
[2] A. Valotta, L. Malihan-Yap, K. Hinteregger, R. Kourist, H. Gruber-Woelfler, ChemSusChem. 2022, 15, e202201468