Decoding Polyurethane Breakdown: A QM/MM MD Exploration of UMG-SP3 Urethanase Catalysis
6 affiliations
- 1LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências Universidade do Porto, Rua do Campo Alegre, s/n, Porto, Portugal, 4169-007
- 2EnZync Center for Enzymatic Deconstruction of Thermoset Plastics
- 3Department of Biotechnology and Biomedicine
- 4Technical University of Denmark
- 5Danish technological Institute
- 6Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, Aarhus, Denmark, DK-8000
Abstract
Polyurethane (PU) low-cost production and versatility propelled its widespread daily usage. However, due to a lack of efficient end-of-life waste treatment options, this recalcitrant polymer tends to accumulate, becoming hazardous. Enzyme depolymerization emerged as a promising 2 alternative to tackle this global problem. Accordingly, three metagenome-based urethanases were discovered (UMG-SP1, 2 and 3). Despite several efforts being made to understand their catalysis, none of the studies accounted for full protein sampling. To address this, we employed an umbrella sampling-based quantum mechanics/molecular mechanics methodology to explore UMG-SP3catalyzed urethane bond hydrolysis. Our results revealed that the hydrolytic mechanism occurred in two sequential stages: i) acylation; and ii) deacylation. The first stage was rate-limiting, with an energetic barrier of 21.6 kcal.mol-1, corresponding to the formation of the acyl-enzyme state and the release of an alcohol (leaving group). Remarkably, the energetic barrier was in agreement with the previously reported values for the UMG-SP2 homolog. In addition, the enzyme shown preference for the cleavage of the C-O bond instead of the C-N bond. However, we observed that the overall reaction was endergonic, with a product-state Gibbs free energy of 8.3 kcal.mol-1. UMG-SP3 has previously been shown to be less stable than the other UMG-SPs. As a result, its more mobile active site may be less effective at stabilizing the released product, increasing the associated free energy. Hence, to improve the likelihood of industrial implementation, the mechanistic data should be leveraged to rationally engineer a more stable and efficient enzyme. Altogether, these findings can pave the way for improving enzymatic depolymerization of PU.
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BibTeX
@misc{teixeira2026decoding,
title = {{Decoding Polyurethane Breakdown: A QM/MM MD Exploration of UMG-SP3 Urethanase Catalysis}},
author = {Luís M. C. Teixeira and Pedro Paiva and Alexander Sandahl and J. Preben Morth and Peter Westh and Daniel E. Otzen and Pedro A. Fernandes and Maria J. Ramos},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009977/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009977/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Decoding Polyurethane Breakdown: A QM/MM MD Exploration of UMG-SP3 Urethanase Catalysis
AU - Luís M. C. Teixeira
AU - Pedro Paiva
AU - Alexander Sandahl
AU - J. Preben Morth
AU - Peter Westh
AU - Daniel E. Otzen
AU - Pedro A. Fernandes
AU - Maria J. Ramos
PY - 2026
DA - 2026/10/06
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009977/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009977/v1
AB - Polyurethane (PU) low-cost production and versatility propelled its widespread daily usage. However, due to a lack of efficient end-of-life waste treatment options, this recalcitrant polymer tends to accumulate, becoming hazardous. Enzyme depolymerization emerged as a promising 2 alternative to tackle this global problem. Accordingly, three metagenome-based urethanases were discovered (UMG-SP1, 2 and 3). Despite several efforts being made to understand their catalysis, none of the studies accounted for full protein sampling. To address this, we employed an umbrella sampling-based quantum mechanics/molecular mechanics methodology to explore UMG-SP3catalyzed urethane bond hydrolysis. Our results revealed that the hydrolytic mechanism occurred in two sequential stages: i) acylation; and ii) deacylation. The first stage was rate-limiting, with an energetic barrier of 21.6 kcal.mol-1, corresponding to the formation of the acyl-enzyme state and the release of an alcohol (leaving group). Remarkably, the energetic barrier was in agreement with the previously reported values for the UMG-SP2 homolog. In addition, the enzyme shown preference for the cleavage of the C-O bond instead of the C-N bond. However, we observed that the overall reaction was endergonic, with a product-state Gibbs free energy of 8.3 kcal.mol-1. UMG-SP3 has previously been shown to be less stable than the other UMG-SPs. As a result, its more mobile active site may be less effective at stabilizing the released product, increasing the associated free energy. Hence, to improve the likelihood of industrial implementation, the mechanistic data should be leveraged to rationally engineer a more stable and efficient enzyme. Altogether, these findings can pave the way for improving enzymatic depolymerization of PU.
ER -