Design of an electrochemical bioproduction system for piperazines

This interdisciplinary research project between the groups of Prof. Dr Bernhard Hauer/Dr. Bettina Nestl (University of Stuttgart/ Innophore), Prof. Dr. Ulf-Peter Apfel (UMSICHT; RUB) and Dr. Lars Lauterbach (RWTH Aachen) addresses two fundamental areas of Priority Program 2240, namely metabolic engineering of microorganisms for electro-biosynthesis of value-added products and electrode and reactor engineering for efficient bio-electrochemical processes. The CO2-fixing and H2-oxidizing Knallgas microorganism Ralstonia eutropha represents a versatile platform organism for producing various chemicals and biopolymers. Nitrogen-containing heterocycles such as piperazines are highly valuable building blocks found in multiple medicinal and bioactive natural products. The lack of efficient methods for direct synthesis of C- and N-substituted piperazines is one of the significant hurdles in realizing 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 expensive cofactor NADPH, which must be continuously recycled for practical large-scale applications. In this project, we aim to develop a stackable PEM-like reactor that combines the CO2 fixation metabolism of R. eutropha with the electro-driven supply of reducing equivalents for the continuous flow synthesis of piperazines.

Project overview