Beyond the Catalytic Serine: Selective Protease Engagement with

Covalent Macrocyclic Activity-Based Probes

M. Barrueco, E. Hyde, E. Sawtell, J. Mills, V. Nikoloudi, M.

Enget, M. Laabei, M. Lakemeyer, S. Lovell, BioRxiv, doi.org/10.64898/2026.05.20.726481

Multi-omics studies reveal how ambient temperature changes govern cellular responses of Chlamydomonas
P. Shetty, T. Vuong, C. Li, V. Wagner, D. Myrzakhmetova, C.-C. Peng,  W. Li, , J. Ching, A. Zander, S. Weiser, R. J. Allen, M. Lakemeyer, M. Mittag, The Plant Cell, in press.

Microbial DL-Peptidases Enable Predator Defense and Facilitate Structure Elucidation of Complex Natural Products
B. Zhang, Y. Huang, K. Schlabach, M.A. Tran, R. Nachawati, N. Bader, A. Komor., C. Hertweck, H. Schindelin, M. Lakemeyer*, U.A. Hellmich*, P. Stallforth*, J. Am. Chem. Soc., 148, 5, 5264–5274.
*co-corresponding authors

A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation
M. Lakemeyer,* R. Latorre, K. Blazkova, H. M. Wood, D. Jensen, N. Shakil, S. C. Thomas, D. Saxena, Y. Mulpuri, D. Poolman, P. Duran, L. J. Keller, D. E. Reed, B. L. Schmidt, N. N. Jiménez-Vargas, F. Xu, A. E. Lomax, N. W. Bunnet*, and M. Bogyo*,
Cell Host Microbe, 33, 1686–1702.e11.
*co-corresponding authors

Inhibitor fluorination pattern tunes chemically induced protein dimerization
E. Schwegler, J.-M. Harder, M. Preuss, C. Guhl, S. Zhang, A. Wagner, N. Bader, P. Stallforth, M. Lakemeyer, H. Schindelin, T. Opatz, Ute A. Hellmich,
BioRxiv, doi.org/10.1101/2025.07.23.666362.

Funktionelle Charakterisierung unbekannter Proteasen des Mikrobioms
N. Shakil, M. Lakemeyer
BIOspektrum, doi.org/10.1007/s12268-025-2403-2

Funktionelle Charakterisierung der Darmflora und ihrer hydrolytisch aktiven Enzyme - Trendbericht Biochemie
J. Seidel, M. Lakemeyer, Nachrichten aus der Chemie, doi.org/10.1002/nadc.20244143493

Structure of Staphylococcus aureus ClpP Bound to the Covalent Active Site Inhibitor Cystargolide A
A. Illigmann*, M.-T. Vielberg*, M. Lakemeyer*, F. Wolf, T. Dema, P. Stange, W. Kuttenlochner, E. Liebhart, A. Kulik, N. Staudt, I. Malik, S. Grond, S. A. Sieber, L. Kaysser, M. Groll, H. Brötz-Oesterhelt, Angew. Chem. Int. Ed. 63, e202314028.

Chemoproteomic identification of a dipeptidyl peptidase 4 (DPP4) homolog in Bacteroides thetaiotaomicron important for envelope integrity and fitness 
L. J. Keller, T. H. Nguyen, L. Liu, M. Lakemeyer, D.J. Gelsinger, R. Chanin, N. Ngo, K. M. Lum, F. Faucher, P. Ipock, M. J. Niphakis, A. S. Bhatt, A. J. O’Donoghue, K. C. Huang, M. Bogyo, Nat. Chem. Bio., 19, 1469–1479.

Antibiotic acyldepsipeptides stimulate the Streptomyces ClpP-ATPase/ClpP complex for accelerated proteolysis

L. Reinhard, D. Thomy, M. Lakemeyer, J. Ortega, S. Sieber, P. Sass, H. Brötz-Oesterhelt, mBio, 13, e01413-22.

Uncovering an overlooked consequence of phosphorylation: change in cysteine reactivity
M. Lakemeyer, M. Bogyo, Nat. Methods, 19,  281–283.

Integration of bioinformatic and chemoproteomic tools for the study of enzyme conservation in closely related bacterial species

L. J. Keller, M. Lakemeyer, M. Bogyo, Methods in Enzymol., 664, 1–22.

Toxoplasma gondii serine hydrolases regulate parasite lipid mobilization during growth and replication within the host
O. Onguka, B. M. Babin, M. Lakemeyer, I. T. Foe, N. Amara, S. M. Terrell, K. Lum, P. Cieplak, J. Z. Long, M. Bogyo, Cell Chem. Biol., 28, 1501–1513. 

Activity-based protein profiling in bacteria: Applications for identification of therapeutic targets and characterization of microbial communities
L. J. Keller, B. M. Babin, M. Lakemeyer, M. Bogyo, Curr. Opin. Chem. Biol., 54, 45–53.

Tailored peptide phenyl esters block ClpXP proteolysis by an unusual breakdown into a heptamer-hexamer assembly
M. Lakemeyer, E. Bertosin, F. Möller, D. Balogh, R. Strasser, H. Dietz, S.A. Sieber, Angew. Chem. Int. Ed. Engl., 58, 7127–7132.

Thinking outside the box: novel antibacterials to tackle the resistance crisis
M. Lakemeyer, W. Zhao, F. A. Mandl, P. Hammann, S.A. Sieber, Angew. Chem. Int. Ed. Engl., 57, 14440–14475.

Design and synthesis of tailored human caseinolytic protease P inhibitors
T. F. Gronauer, M. M. Mandl, M. Lakemeyer, M. W. Hackl, M. Meßner, V. S. Korotkov, J. Pachmayr, S. A. Sieber, Chem. Commun. (Camb.), 54, 9833–9836.

Quantitative map of beta-lactone induced virulence regulation
J. Krysiak, M. Stahl, J. Vomacka., C. Fetzer, M. Lakemeyer, A. Fux, S.A. Sieber,  J. Proteome. Res., 16, 1180–1192.

Reversible inhibitors arrest ClpP in a defined conformational state that can be revoked by ClpX association
A. Pahl*, M. Lakemeyer*, M.-T. Vielberg*, M.W. Hackl, J. Vomacka, V.S. Korotkov, M. Stein, C. Fetzer, K. Lorenz-Baath, K. Richter, H. Waldmann, M. Groll, S.A. Sieber, Angew. Chem. Int. Ed. Engl., 54, 15892–15896.

Phenyl esters are potent inhibitors of caseinolytic protease P and reveal a stereogenic switch for deoligomerization
M.W. Hackl*, M. Lakemeyer*, M. Dahmen, M. Glaser, A. Pahl, K. Lorenz-Baath, T. Menzel, S. Sievers, T. Böttcher, I. Antes, H. Waldmann, S.A. Sieber, J. Am. Chem. Soc., 137, 8475–8483.

* These authors contributed equally to the work.