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.
Publications
Borlinghaus N, Gergel S, Nestl BM (2018) Biocatalytic access to piperazines from diamines and dicarbonyls. ACS Catalysis, 8(4):3727-32. https://doi.org/10.1021/acscatal.8b00291
Al‐Shameri A, Petrich MC, Junge Puring K, Apfel UP, Nestl BM, Lauterbach L (2020) Powering artificial enzymatic cascades with electrical energy. Angewandte Chemie International Edition, 59(27):10929-33. https://doi.org/10.1002/anie.202001302
Stockinger P, Borlinghaus N, Sharma M, Aberle B, Grogan G, Pleiss J, Nestl BM (2021) Inverting the stereoselectivity of an NADH-dependent imine-reductase variant. ChemCatChem, 13, 5210. https://doi.org/10.1002/cctc.202101057
People

Univ.-Prof. Dr. Lars Lauterbach
RWTH Aachen
Institute for Applied Microbiology

Prof. Dr. Bernhard Hauer
University of Stuttgart
Institute of Systems Biotechnology

Dr. Bettina Nestl
University of Stuttgart
Institute of Systems Biotechnology

Prof. Dr. Ulf-Peter Apfel
Ruhr-Universität Bochum
Chair of Inorganic Chemistry I

Ramineh Rad
Ruhr-Universität Bochum

Pierre Schoenmakers
RWTH Aachen
Institute for Applied Microbiology

Benjamin Aberle
University of Stuttgart
Institute of Systems Biotechnology