Next Generation electroenzymatic cascades for complex molecules (NGeCascades)

The aurachins constitute a large family of isoprenoid quinolone antibiotics isolated from the myxobacteria Stigmatella aurantiaca and S. erecta. Their biosynthesis has been investigated by feeding studies as well as genetic experiments revealing anthranilic acid and acetate as precursors. Due to their structure and biological activity, the aurachins represent a good model system to study the integrated use of organic synthesis, biocatalysis and electroenzymatic ATP supply. Each individual system of this cascade, the electroorganic synthesis of an N-hydroxyquinolone library, the prenylation of these derivatives with a recombinant prenyltransferase to aurachin derivatives as well as an electroenzymatic production of ATP has not been described previously and is in itself of high novelty. Moreover, such a combination is unprecedented for the synthesis of such complex molecules. Therefore, fundamental questions of compatibility and engineering of the cascade are raised and will be investigated by this project in addition to establishing the individual reaction steps.

Publications

Wirtanen T, Prenzel T, Tessonnier JP, Waldvogel SR (2021) Cathodic corrosion of metal electrodes—how to prevent it in electroorganic synthesis. Chemical Reviews, 6;121(17):10241-70. https://doi.org/10.1021/acs.chemrev.1c00148

Siedentop R, Claaßen C, Rother D, Lütz S, Rosenthal K (2021) Getting the Most Out of Enzyme Cascades: Strategies to Optimize In Vitro Multi-Enzymatic Reactions. Catalysts, 11(10):1183. https://doi.org/10.3390/catal11101183

Siedetop R, Rosenthal K (2022) Industrially Relevant Enzyme Cascades for Drug Synthesis and Their Ecological Assessment. International Journal of Molecular Sciences, 23(7):3605. https://doi.org/10.3390/ijms23073605

Kinner A, Nerke P, Siedentop R, Steinmetz T, Classen T, Rosenthal K, Nett M, Pietruszka J, Lütz S (2022) Recent Advances in Biocatalysis for Drug Synthesis. Biomedicines, 10(5):964. https://doi.org/10.3390/biomedicines10050964

Kruth S, Schibajew L, Nett M (2022) Biocatalytic production of the antibiotic aurachin D in Escherichia coli. AMB Expr, 12, 138. https://doi.org/10.1186/s13568-022-01478-8

Winter J, Prenzel T, Wirtanen T, Schollmeyer D, Waldvogel SR (2022) Direct Electrochemical Synthesis of 2,3‐Disubstituted Quinoline N‐oxides by Cathodic Reduction of Nitro Arenes. Chemistry–A European Journal, 29(12):e202203319. https://doi.org/10.1002/chem.202203319

Kruth S, Zimmermann CJ-M, Kuhr K, Hiller W, Lütz S, Pietruszka J, Kaiser M, Nett M (2023) Generation of Aurachin Derivatives by Whole-Cell Biotransformation and Evaluation of Their Antiprotozoal Properties. Molecules, 28(3):1066. https://doi.org/10.3390/molecules28031066

Siedentop R, Dziennus M, Lütz S, Rosenthal K (2023) Debottlenecking of an In Vitro Enzyme Cascade Using a Combined Model- and Experiment-Based Approach. Chemie Ingenieur Technik. https://doi.org/10.1002/cite.202200170

Koleda O, Prenzel T, Winter J, Hirohata T, de Jesús Gálvez-Vázquez M, Schollmeyer D, Inagi S, Suna E, Waldvogel SR (2023) Simple and scalable electrosynthesis of 1H-1-hydroxy-quinazolin-4-ones. Chemical Science, 14(10):2669-75. https://doi.org/10.1039/D3SC00266G

Siedentop R, Siska M, Möller N, Lanzrath H, von Lieres E, Lütz S, Rosenthal K (2023) Bayesian Optimization for an ATP-Regenerating In Vitro Enzyme Cascade. Catalysts, 23;13(3):468. https://doi.org/10.3390/catal13030468

Kruth S, Nett M (2023) Aurachins, Bacterial Antibiotics Interfering with Electron Transport Processes. Antibiotics, 12(6):1067. https://doi.org/10.3390/antibiotics12061067