Project Details
Projekt
Next Generation electroenzymatic cascades for complex molecules (NGeCascades)
Applicants
Professor Dr. Stephan Lütz; Professor Dr. Markus Nett; Professor Dr. Siegfried R. Waldvogel
Subject Area
Biological Process Engineering
Biological and Biomimetic Chemistry
Organic Molecular Chemistry - Synthesis and Characterisation
Biological and Biomimetic Chemistry
Organic Molecular Chemistry - Synthesis and Characterisation
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 445751305
Up to now, electroenzymatic synthesis has mainly focused on the (re)generation of redox cosubstrates and cofactors. Furthermore, its use was mostly limited to single or two-step bio-transformations. However, electrochemistry is also an elegant tool for the supply of high-energy, non-redox cofactors, such as ATP and ATP-derived pyrophosphates, which are essential for several biosynthetic reactions. In this project, electroenzymatic synthesis will be used to fuel the production of valuable biomolecules with both, their chemical building blocks and the required cofactor ATP. The aurachin family of natural products will illustrate the synthetic utility of electroenzymatic cascades e.g. for carbon-carbon bond formation. Biosynthetically, the aurachins originate from the linkage of an anthranilate-derived quinolone N-oxide moiety with farnesyl pyrophosphate (FPP). The enzymatic reaction sequence, which leads to FPP, consumes several molecules of ATP and will serve as an exemplary model for the electroenzymatic preparation of the “universal energy carrier”. Moreover, the quinolone building block represents an interesting target in order to develop novel biomimetic electrochemical synthesis routes and for generating derivatives. Such analogs will provide an entry point for the directed in vivo and in vitro biosynthesis of custom-made aurachins for structure-activity relationship studies. From a medicinal chemistry perspective, this approach is highly attractive, considering the potent antibacterial and antiplasmodial properties of the aurachins. As ATP and ATP-derived energy carriers are ubiquitous in biosynthesis, the insights gained in this project will be broadly useful in the field of electroenzymatic synthesis. This study might also serve as a blueprint for the construction of artificial metabolic pathways in future bio(electrochemical) systems.
DFG Programme
Priority Programmes
