In MetaProcess, we aim to establish and optimize a stable, efficient, and economically sustainable biocatalytic workflow for chiral amino alcohol production. In the project, the synthesis of metaraminol, which is an adrenergic receptor agonist used as a vasoconstrictor, will be used as an exemplary and industrially relevant showcase. Synthesis pathways for metaraminol and related amino alcohols have relied on classic chemistry, based on petrochemical resources and metal-based catalysis reactions. We have shown in the past that the biosynthesis of metaraminol can be achieved by combining an enzymatic carboligation step and a subsequent reductive amination step, catalyzed by an amine transaminase. It is remarkable that the process can be applied over readily available second‑generation feedstocks such as xylose and glucose, making it environmentally friendly and sustainable, while also having a high yield and high chemo- and stereoselectivity. However, for an economically and ecological efficient process on larger (industrial) scale, the biocatalyst must be reused. While immobilization is efficient and enables immensely enhanced specific space-time yields of the overall cascade due to repetitive enzyme use, further process intensification is limited by the operational stability of the applied biocatalysts.
In MetaProcess, we will use a multidisciplinary approach to generate stable carboligase and transaminase variants, able to withstand repetitive batch/continuous production of amino alcohols, such as metaraminol and methoxamine, in a longer time scale. Rational design and directed evolution will be used to identify optimized variants, which will be integrated into a comprehensive industrial workflow for chiral amino alcohol production. Here, continuous reactions are applied in a cascaded flow process to generate a scalable procedure. This includes integrated downstream processing by effective in situ product removal. The developed platform will be evaluated through techno-economic analysis and a life cycle assessment (LCA), allowing to identify parameter sensitivities and evaluate sustainability and economic feasibility. We foresee obtaining a scalable and ready-to-use lab-scale demonstrator plant that makes amino alcohol production more sustainable and efficient, ultimately lowering the access barrier for otherwise challenging to obtain (chemical) building blocks and active pharmaceutical ingredients (APIs).
Dr. Stephan Schott-Verdugo
Prof. Dr. Gohlke, Computational Pharmaceutical Chemistry and Molecular Bioinformatics, HHU Düsseldorf
Prof. Dr. Rother, IBG-1: Systems Biotechnology, Forschungszentrum Jülich/ RWTH Aachen
Prof. Dr. Jupke, AVT.FVT - Fluid Process Engineering, RWTH Aachen
Prof. Dr. Schwaneberg & Dr. Anna Joelle Ruff, Chair of Biotechnology, RWTH Aachen