EnzymAgglo – Multiscale model-based investigation of enzyme clusters and agglomerates for cascade bioreactions

Figure 1: Visual representation of multi-enzyme complexes forming agglomerates.

In biotechnology and bioprocess engineering, the formation of stable enzyme clusters and agglomerates for bioreactions is of highest interest [1]. Enzymatic biocatalysis enables efficient reaction pathways, which are essential for many processes in nature and technology.

To date, the formation of catalytically active enzyme clusters and agglomerates, although experimentally observed [2], is hardly understood. No model is available to predict the formation and stability of enzyme clusters and agglomerates, as well as their influence on overall catalytic performance. Understanding these processes, however, is crucial to allow for targeted modification and optimization.

The objective of this project is the development of a multi-scale model framework and its validation by experimental characterization to describe the dynamics and function of multi-enzyme complex clusters and agglomerates. For this, various modeling techniques from molecular dynamics (MD) [3-4] to the discrete element method (DEM) [5-7] are being coupled to bridge the vast differences in time scale and length, ranging from Angstrom to the millimeter scale. Experimental validation is obtained by cell-based and cell-free expression of enzymes and their mutants, as well as their characterization, e.g. activity and enzyme-enzyme interactions. As a model enzyme, the Pyruvate Dehydrogenase Complex (PDC) is used, which combines properties like coupled multi-step reactions, cofactor regeneration, metabolic channeling and dynamic self-assembly to large catalytic clusters and thus builds up a unique macromolecular bioconversion machinery. A visual schematic of multi-enzyme complex agglomeration is depicted in Figure 1.


The authors are grateful to the Deutsche Forschungsgemeinschaft (DFG) for financial support (SPP 1934) and would like to thank all project partners.


  1. Castellana M., Wilson M.Z., Xu Y., Joshi P., Cristea I.M., Rabinowitz J.D., … & Wingreen N. S. (2014). Nature Biotechnology, 32(10), 1011-1018.
  2. Guo, J., Hezaveh, S., Tatur, J., Zeng, A. P., & Jandt, U. (2017). Biochemical Journal, 474(5), 865-875.
  3. Hezaveh S., Zeng A.P., Jandt U. (2016). J. Phys. Chem. B, 120(19), 4399-4409
  4. Hezaveh S., Zeng A.P., Jandt U. (2017). ACS Omega, 2(3), 1134-1145.
  5. Dosta M., Antonyuk S., Heinrich S. (2013). Industrial Engineering Chemistry Research, 52(33), 11275-11281.
  6. Spettl A., Dosta M., Antonyuk S., Heinrich S., Schmidt V. (2015). Adv. Powder Techn., 26(3), 1021-1030.
  7. Schnegas S., Antonyuk S., Heinrich S. (2015). Powder Techn., 237, 529-536.

responsible institutes:

Institute of Solids Process Engineering and Particle Technology
Technische Universität Hamburg
Denickestraße 15
21073 Hamburg
Institute of Bioprocess and Biosystems Engineering
Technische Universität Hamburg
Denickestraße 15
21073 Hamburg
position name e-mail phone
Project supervisor Prof. Stefan Heinrich stefan.heinrich@tuhh.de +49(0)40-428783750
Project supervisor Prof. Maksym Dosta dosta@tuhh.de +49(0)40-428783564
Project employee Nicolas Depta nicolas.depta@tuhh.de +49(0)40-428782765
Project supervisor Prof. An-Ping Zeng aze@tuhh.de +49(0)40-428784183
Project supervisor Dr. Uwe Jandt uwe.jandt@tuhh.de +49(0)40-428782847
Project employee Sibel Ilhan sibel.ilhan@tuhh.de +49(0)40-428782694

◄ Zurück zu Projekten