Investigation of complex amino acid- and amine-based in situ-product crystallization strategies in transaminase- and amine dehydrogenase-catalyzed reactions and its development towards flow reaction concepts

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Transaminases are very versatile, selective biocatalysts for the synthesis of relevant chiral amines. Unfortunately various applications of these biocatalysts suffer from poor reaction equilibria, which result in low atom efficiencies for the asymmetric synthesis. This problem is typically compensated by effortful strategies, e.g. by complex cascade reaction with multiple biocatalysts, an over-stoichiometric use of the donor amine or specific amines with non-enzymatic side reactions.The presented project targets directly the reaction equilibrium limitation with an integrated process concept by an in situ-crystallization of the product amine from the reaction mixture. The crystallization of the product amine is facilitated by the formation of a barely soluble salt, which is then continuously removed from the reaction mixture. This effect shifts the position of equilibrium towards the products and simultaneously allows a simplified product isolation procedure by filtration. This concept will be eventually converted into a continuous process at multi-gram scale including a full recycle of the non-converted substrates to improve the overall atom efficiency of the biocatalytic reaction. The proposed project is structured into 7 work packages and 2 milestones, which span the work flow from the early screening of suitable acids to the final optimized reaction concept at larger scale. After the selection of applicable acids the salt pairs will be characterized and the reaction conditions optimized for various transaminases. Subsequently a scale-up including a continuous reaction concept will be validated. The project is completed with the investigation of a potential crystallization of the co-product pyruvate, which yields an analogous shift of the position of the reaction equilibrium.