Research Highlights

Dr. Andy-Mark Thunnissen

Three top publications 2017-2022

1. Xu GC, Kunzendorf A, Crotti M, Rozeboom HJ, Thunnissen AMWH & Poelarends GJ (2022) Gene fusion and directed evolution to break structural symmetry and boost catalysis by an oligomeric C-C bond-forming enzyme. Angewandte Chemie International Edition 61: e202113970; DOI: https://doi.org/10.1002/anie.202113970.

A highly effective gene fusion strategy was adopted to evolve a homohexameric tautomerase into an efficient and enantioselective “Michaelase”. Crystallographic analysis provided unique insights into the structural basis for the enhanced enzymatic activity.

2. Meng QL, Capra N, Palacio CM, Lanfranchi E, Otzen M, van Schie LZ, Rozeboom HJ, Thunnissen AMWH, Wijma HJ & Janssen DB (2020) Robust omega-transaminases by computational stabilization of the subunit interface. ACS Catalysis 10: 2915-2928; DOI: https://doi.org/10.1021/acscatal.9b05223.

Prominent demonstration of the effectiveness of the FRESCO protocol for increasing enzyme stability, by integrating computational design and "in-silico" testing of smart mutant libraries with experimental validation and structural analysis.

3. Villarino L, Splan KE, Reddem E, Alonso-Cotchico L, de Souza CG, Lledos A, Marechal JD, Thunnissen AMWH & Roelfes G (2018) An artificial heme enzyme for cyclopropanation reactions. Angewandte Chemie International Edition 57: 7785-7789; DOI: https://doi.org/10.1002/anie.201802946.

An artificial heme enzyme was created which displayed good activity despite its crystal structure suggesting inaccessibility for substrates. Molecular dynamics simulations revealed dynamic structural changes that allowed substrate binding and pre-catalytic structure formation.