Design of Plastic-Degrading Enzymes

Molecular interaction model of Polyester Hydrolase Leipzig 7 (PHL7) with a PET surface. PHL7 is promising candidate for an industrially used PETase enzyme and can efficiently degrade PET in post-consumer plastic. In our research, we use computer-aided protein design to engineer new variants of PHL7 with higher stability and activity.

The widespread use of plastics has led to a significant accumulation of non-biodegradable waste in the environment. Current recycling methods for synthetic plastics, like polyethylene terephthalate (PET), a thermoplastic polymer that is widely used in the food packaging industry, are not sustainable and have a high energy consumption. Enzymatic catalysis is a sustainable recycling solution because it does not require harsh chemicals, high temperature or pressure. However, there is still a gap preventing enzymes to scale to widespread industrial usage:  1) Current enzymes have limited stability and temperature dependence. 2) Current enzymes do not have an ideal pH and buffer dependence. 3) Enzyme activity is not optimized for industrial reaction conditions.
To address these gaps our research group designs plastic degrading enzymes that have optimized properties for an industrial usage. To achieve this, we use a combination of Rosetta protein design, machine learning directed evolution, molecular dynamics, and deep learning methods. Designed enzymes are produced and tested in the wet lab. Furthermore, X-ray crystallography is used to determine the structure of novel enzymes and obtain important insight into the enzyme reaction mechanism.

Selected Publications:

  • Engelberger F, Zakary JD, Künze G. Guiding protein design choices by per-residue energy breakdown analysis with an interactive web application. Front Mol Biosci. 2023. 10:1178035. doi: 10.3389/fmolb.2023.1178035
  • Falkenstein P, Zhao Z, Di Pede-Mattatelli A, Künze G, Sommer S, Sonnendecker C, Zimmermann W, Colizzi F, Matysik J, Song C. On the Binding Mode and Molecular Mechanism of Enzymatic Polyethylene Terephthalate Degradation. ACS Catalysis. 2023. 13:6919-6933, doi: 10.1021/acscatal.3c00259
  • Richter PK, Blázquez-Sánchez P, Zhao Z, Engelberger F, Wiebeler C, Künze G, Frank R, Krinke D, Frezzotti E, Lihanova Y, Falkenstein P, Matysik J, Zimmermann W, Sträter N, Sonnendecker C. Structure and function of the metagenomic plastic-degrading polyester hydrolase PHL7 bound to its product. Nat Commun. 2023. 14(1):1905. doi: 10.1038/s41467-023-37415-x


Collaborations:

Dr. Christian Sonnendecker, Institute of Analytical Chemistry, ESTER Biotech, University of Leipzig
Prof. Dr. Norbert Sträter, Center for Biotechnology and Biomedicine, Institute of Bioanalytical Chemistry, University of Leipzig