Max Crüsemann, PhD
Heisenberg group leader
Research
Our group is interested in the discovery and biosynthesis of natural products. Compounds isolated from various terrestrial and marine sources such as bacteria, fungi and plants harbor enormous structural diversity and often exhibit strong, e.g. antibiotic or cytotoxic biological activities. Thus, it is not surprising that more than half of all approved drugs in human use are or are derived from natural products. For the development of new drugs, it is therefore still very important to find and characterize natural products with innovative activities, modes of actions and structural features.
Since traditional cultivation and isolation approaches frequently only lead to rediscovery of known compounds, we apply interdisciplinary, “omics”-based approaches to discover novel and bioactive natural products from underexplored sources. Genome sequencing and the development of powerful bioinformatic approaches has revealed that many bacteria harbor a large number of uncharacterized biosynthetic pathways, organized in gene clusters. This procedure is called “genome mining”. We use state-of-the-art synthetic biology methods to directly capture and express prioritized gene clusters in heterologous hosts, followed by structure elucidation and bioactivity evaluation. In addition, natural product producers can be forced to produce the compounds of interest by environmental challenges or genetic manipulation of the gene cluster of interest. We routinely employ innovative mass spectrometry-based approaches that aid in the rapid dereplication of natural products from complex mixtures and the optimization of different experimental production conditions.
Natural products biosynthesis often embodies fascinating and highly effective biochemical reactions. We interrogate selected natural product pathways in detail by analyzing important biosynthetic steps with heterologously expressed and purified enzymes in vitro, complemented by in vivo experiments in the natural products producers. The obtained insights into the biosyntheses of complex natural products will help us to engineer these biosynthetic pathways for the generation of novel compounds with improved structural or biological activities.
One of our main projects deals with the potent G protein inhibitor FR900359 (FR). In the last years, we have been studying the biosynthesis of this complex nonribosomal cyclic depsipeptide natural product in plant-associated bacteria. Two of our works were recently highlighted on journal covers:
Institut of Pharmaceutical Biology
Workgroup Crüsemann
CV
3/2013-4/2015:
Postdoctoral research studies with Prof. Bradley Moore, Scripps Institution of Oceanography, UC San Diego
5/2015-3/2017:
Senior postdoctoral research scientist in the group of Prof. Gabriele König, University of Bonn
4/2017:-11/2023:
Junior research group leader in the Institute of Pharmaceutical Biology, University of Bonn
Since 12/2023:
Heisenberg group leader in the Institute of Pharmaceutical Biology, University of Bonn
2003-2007:
Studies of Pharmacy at Philipps-University, Marburg
11/2007-4/2008:
Practical pharmacy training at Tiergarten-Apotheke, Konstanz
5/2008-2/2009:
Diploma thesis: "Isolierung und Charakterisierung biogener Inhaltsstoffe von Pittosporum angustifolium", with Prof. Ulrike Lindequist, University of Greifswald
12/2008:
Approbation to licensed pharmacist
3/2009-7/2012:
PhD studies in the group of Prof. Jörn Piel, University of Bonn.
7/2012:
Promotion to Dr. rer. nat. (grade: 1.0, magna cum laude) “Studies on the biosynthesis of hormaomycin”
- DPhG
- VAAM
- DECHEMA
Projects/Third-party funds
FOR2372 - Project 1
Duration
2016 - 2023
Founder:
DFG
GRK2873
Duration:
2023 - 2027
Founder:
DFG
RESIDE
Duration:
2023 - 2026
Founder:
DFG
Awards
DECHEMA Award for Young Scientists
Year:
2024
Award for:
Research on natural products
Heisenberg scholarship
Year:
2023
Award for:
Outstanding science
Award of the DPhG-Stiftung
Year:
2022
Award for:
Young Scientists
Biosynthesis of the corallorazines, a widespread class of antibiotic cyclic lipodipeptides
Dreckmann, T.M., Fritz, L., Kaiser, C.F., Bouhired, S.M., Wirtz, D.A., Rausch, M., Müller, A., Schneider, T., König, G.M., Crüsemann, M.
RSC Chem Biol. 2024 Aug 16
Highlighted by several media (e.g. GEO, MDR)
Featured on Journal Cover
Selected publications
Adenylation domain-guided recruitment of trans acting non-heme monooxygenases in nonribosomal peptide biosynthesis
Wirtz, D.A., Schneberger, N., Klöppel, S., Richarz, R., Geyer, M., König, G.M., Hagelueken, G., Crüsemann, M.*
ACS Chem Biol 2023, Jun 27
Featured on Journal Cover
A specialized dehydrogenase provides l-phenyllactate for FR900359 biosynthesis
Klöppel, S., Richarz, R., Wirtz, D.A., Vasenda, N., König, G.M., Crüsemann, M.*
Chembiochem 2022 23, e202100569
Highlighted as “VIP paper”, Featured on Journal Cover
The Chromodepsins: Chemistry, Biology and Biosynthesis of a Gq-inhibiting Natural Product Family
Hermes, C., König, G.M., Crüsemann, M.*
Nat Prod Rep 2021 38, 2276-2292
Selected publications
Biosynthesis and mechanism of action of the cell wall targeting antibiotic hypeptin
Wirtz, D.A., Ludwig, K.C., Arts, M., Marx, C.E., Krannich, S., Barac, P., Kehraus, S., Josten, M., Henrichfreise, B., Müller, A., König, G.M., Peoples, A.J., Nitti, A., Spoering, A.L., Ling, L.L., Lewis, K., Crüsemann, M.*, Schneider T.*
Angew Chem Int Ed 2021 60, 13579-13586
*= co-corresponding author
Thioesterase-mediated Side Chain Transesterification Generates Potent Gq Signaling Inhibitor FR900359
Hermes, C., Richarz, R., Wirtz, D.A., Patt, J., Hanke, W., Kehraus, S., Voß, J.H., Küppers, J., Ohbayashi, T., Namasivayam, V., Alenfelder, J., Inoue, A., Mergaert, P., Gütschow, M., Müller, C.E., Kostenis, E., König, G.M., Crüsemann, M.*
Nat Commun 2021 12, 144
Highlighted by several media (e.g. GEO, MDR)
Applying Molecular Networking for the Detection of Natural Sources and Analogues of the Selective Gq Protein Inhibitor FR900359
Reher, R., Kuschak, M., Heycke, N., Annala, S., Kehraus, S., Dai, H-F., Müller, C.E., Kostenis, E., König, G.M., Crüsemann, M.*
J Nat Prod 2018 81, 1628-1635
Heterologous expression, biosynthetic studies and ecological function of the selective Gq-signaling inhibitor FR900359
Crüsemann, M., Reher, R., Schamari, I., Brachmann, A.O., Ohbayashi, T., Kuschak, M., Malfacini, D., Seidinger, A., Pinto-Carbó, M., Richarz, R., Reuter, T., Kehraus, S., Hallab, A., Attwood, M., Schiöth, H.B., Mergaert, P., Kikuchi, Y., Schäberle, T.F., Kostenis, E., Wenzel, D., Müller, C.E., Piel, J., Carlier, A., Eberl, L., König, G.M.
Angew Chem Int Ed 2018 57, 836–840
doi: 10.1002/anie.201707996