Institut für Pharmazeutische Wissenschaften
University of Freiburg

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Scientific Portrait

What we work on

Researchers have shown that secondary metabolites are composed of only a few different building blocks of the primary metabolism and are then modified in many ways. This means that despite the structural diversity, biosynthesis is based on only a few basic rules, which can be varied and combined in many ways. Biosynthesis steps in which one reaction can lead to different products play a special role. They represent branching points in biosynthesis.

The research of our group aims at the elucidation of such biosynthetic steps, which are often difficult to perform with chemical methods. Special attention is paid to the generation of metabolic diversity and thus the biocatalytic exploitation of entire substance groups.

Our contribution to DialogProTec

Our research is methodologically broadly based and ranges from bioinformatic gene analyses, genetic engineering work on bacteria, yeasts and filamentous fungi, overexpression of proteins and their purification, enzymological activity assays, isolation of metabolites and their structure elucidation (e.g. LC-MS, NMR, CD, VCD), to chemical syntheses of substrates and reference compounds.

For further research areas in the Müller working group: C-C bond linkage of carbonyl compounds with thiamine-diphosphate-dependent enzymes and stereoselective reduction of imines and C=C double bonds with NAD(P)H-dependent enzymes, see our homepage (www.pharmchem.uni-freiburg.de/....

Project-relevant publications

Hüttel, W. Echinocandins: structural diversity, biosynthesis, and development of antimycotics. Appl Microbiol Biotechnol (2020).
(https://doi.org/10.1007/s00253-020-11022-y).

Hüttel, W., & Müller, M. (2020). Regio-and stereoselective intermolecular phenol coupling enzymes in secondary metabolite biosynthesis. Natural Product Reports. (https://pubs.rsc.org/en/content/articlelanding/2020/np/d0np00010h#!divAbstract).

L. Fürtges, S. Obermaier, W. Thiele, S. Foegen and M. Müller, Diversity in Fungal Intermolecular Phenol Coupling of Polyketides – Regioselective Laccase‐based systems. ChemBioChem, 2019, 20, 1928–1932 (doi.org/10.1002/cbic.201900041).

S. Obermaier and M. Müller, Biaryl-Forming Enzymes from Aspergilli Exhibit Substrate-Dependent Stereoselectivity, Biochemistry, 2019, 58, 2589–2593 (doi.org/10.1002/chem.201705998).

S. Obermaier, W. Thiele, L. Fürtges and M. Müller, Enantioselective Phenol Coupling by Laccases in the Biosynthesis of Fungal Dimeric Naphthopyrones. Angew. Chem. 2019, 58, 9125–9128 (doi.org/10.1002/anie.201903759).

N. Saha, A. Mondal, K. Witte, S. K. Singh, M. Müller and S. M. Husain, Monomeric Dihydroanthraquinones: A Chemoenzymatic Approach and its (Bio)synthetic Implications for Bisanthraquinones, Chemistry – A European Journal, 2018, 24, 1283-1286 (doi.org/10.1002/chem.201705998).

K. G. Hugentobler and M. Müller, Towards semisynthetic natural compounds with a biaryl axis: Oxidative phenol coupling in Aspergillus niger. Bioorg. Med. Chem., 2018, 26, 1374–1377 (doi.org/10.1016/j.bmc.2017.08.008).

Staff

Prof. Dr. Michael Müller,
Head of the subproject