Oral Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Computational Investigation of Oxidative Enzymes for Plastic and Biopolymer Degradation (122160)

Luca Bertini 1 , Carla Orlando 1 2 , Jacopo Vertemara 1 , Giuseppe Zampella 1 , Tiziana Marino 3 , Claudio Greco 2
  1. Dipartimento di Biotecnologie e Bioscienze, Università degli studi di Milano-Bicocca, Milano, Italy
  2. Dipartimento di Scienze dell’Ambiente e della Terra, Università degli studi di Milano-Bicocca, Milano, Italia
  3. Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Rende, Italy

The extensive use of plastic polymers and the accumulation of biopolymer waste, such as chitin, pose severe environmental challenges. Fungal and bacterial oxidative enzymes, including laccases and lytic polysaccharide monooxygenases (LPMOs), both copper enzymes, have emerged as promising biocatalysts for degrading recalcitrant materials like low-density polyethylene (LLDPE) and β-chitin. However, a detailed understanding of their molecular mechanisms remains crucial for optimizing their activity.

 

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In this study, we employ a multi-scale computational approach1 integrating molecular dynamics (MD) simulations, docking, and quantum chemistry methods to investigate the interactions and catalytic mechanisms of these enzymes. Specifically, we analyze the dynamic behavior of Rhodococcus opacus R7 bacterial laccase2 (LMCO2) in LLDPE degradation, with a focus on the Met-loop region3 of LMCO2 and its role in substrate specificity. Previous investigations confirm that LMCO2 can degrade polyethylene; however, the mechanism by which the enzyme interacts with such an inert substrate and activates the sp³ C-H bonds remains unclear. Density functional theory (DFT) investigations suggest that hydrophobic interactions within the binding pocket, along with redox-active copper sites and possible long-range electron transfer pathways, may facilitate substrate binding and oxidation. Additionally, we examine bacterial LPMOs in β-chitin oxidation, focusing on MD investigation of substrate binding providing molecular insights into substrate degradation efficiency. By integrating classical and quantum computational approaches, this study deepens the understanding of the substrate binding and catalytic mechanisms of these copper oxidative enzymes, offering valuable insights into sustainable biocatalytic strategies for plastic and biomass recycling.

  1. Rovaletti, A.; De Gioia, L.; Fantucci, P.; Greco, C.; Vertemara, J.; Zampella, G.; Arrigoni, F.; Bertini, L. Recent Theoretical Insights into the Oxidative Degradation of Biopolymers and Plastics by Metalloenzymes. Int. J. Mol. Sci. 2023, 24, 6368
  2. Zampolli J., Mangiagalli M., Vezzini D., Lasagni M., Ami D., Natalello A., Arrigoni F., Bertini L., Lotti M., Di Gennaro P. Oxidative degradation of polyethylene by two novel laccase-like multicopper oxidases from Rhodococcus opacus R7, Environmental Technology and Innovation, 2023, 32, 103273,
  3. Orlando C., Bellei M., Zampolli J., Mangiagalli M., Di Gennaro P., Lotti M., De Gioia L., Marino T., Di Rocco G., Greco C., Arrigoni F., Bertini L. Comparative analysis of Polyethylene-Degrading Laccases: Redox Properties and Enzyme-Polyethylene Interaction Mechanism. ChemSusChem, 2025, e202402253