Design of an electrochemical bioproduction system for piperazines

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This interdisciplinary research project addresses two fundamental areas of the Priority Program 2240, namely the metabolic engineering of microorganism for electro-biosynthesis of value-added products as well as electrode and reactor engineering for efficient bio-electrochemical processes. The CO2-fixing and H2-oxidising Knallgas microorganism Ralstonia eutropha represents a versatile platform organism to produce various chemicals and biopolymers. Nitrogen-containing heterocycles such as piperazines are highly valuable building blocks found in a wide range of medicinal and bioactive natural products. The lack of efficient methods to directly synthesize C- and N-substituted piperazines represents one of the major hurdles in unleashing the full therapeutic potential of these systems. The NADPH-dependent imine reductases catalyze the reductive coupling of dicarbonyls with diamines to generate the corresponding piperazine products. This reaction requires two equivalents of the costly NADPH cofactor, which needs to be continuously recycled for practical large-scale applications. In this project, we aim to engineer a stackable PEM-like reactor that links the CO2 fixation metabolism of R. eutropha with electrodriven supply of reducing equivalents for the continuous flow synthesis of piperazines.