The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Harnessing protein language model for structure-based discovery of highly efficient and robust PET hydrolases
Open accessPublished version of a preprint
Abstract
Plastic waste, particularly polyethylene terephthalate (PET), presents significant environmental challenges, driving extensive research into enzymatic biodegradation. However, existing PET hydrolases (PETases) are limited by narrow sequence diversity and suboptimal performance. This study introduces VenusMine, a protein discovery pipeline that integrates protein language models (PLMs) with a representation tree to identify PETases based on structural similarity using sequence information. Using the crystal structure of Is PETase as a template, VenusMine identifies and clusters target proteins. Candidates are further screened using PLM-based assessments of solubility and thermostability, leading to the selection of 34 proteins for biochemical validation. Results reveal that 14 candidates exhibit PET degradation activity across 30–60 °C. Notably, a PET hydrolase from Kibdelosporangium banguiense ( Kb PETase) demonstrates a melting temperature (T m ) 32 °C higher than Is PETase and exhibits the highest PET degradation activity within 30 – 65 °C among wild-type PETases. Kb PETase also surpasses FastPETase and LCC in catalytic efficiency. X-ray crystallography and molecular dynamics simulations show that Kb PETase possesses a conserved catalytic domain and enhanced intramolecular interactions, underpinning its improved functionality and thermostability. This work demonstrates a novel deep learning approach for discovering natural PETases with enhanced properties.
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Jahanshahi, D. A., Barzani, M. R. R., Bahram, M., Ariaeenejad, S., & Kavousi, K. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.117640 · Cited by 41
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The diversity of PET degrading enzymes: A systematic review of sequence, structure, and function
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Metadata
- Authors
- Wu, B., Zhong, B., Zheng, L., Huang, R., Jiang, S., Li, M., Hong, L., & Tan, P.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Zheng, Lirong
- Hong, Liang
- Tan, Pan
- Venue
- Nature Communications
- Published
- 2025-07-05
- Volume
- 16
- Issue
- 1
- Pages
- 6211-6211
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12228687
- OpenAlex
- W4412048048
- Cited by
- 50
- References
- 67
- Citations by year
- 2026: 39 · 2025: 11
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Research Square (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (12104295)
- Shanghai Municipal Education Commission
- Science and Technology Commission of Shanghai Municipality
- Shanghai Jiao Tong University (21X010200843)
- Centre Scientifique et Technique du Bâtiment
- National Key Research and Development Program of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- PET hydrolase, polyethylene terephthalate degradation, plastic waste biodegradation, protein language models, thermal stability, catalytic efficiency, protein solubility prediction
- MeSH terms
- Hydrolases, Polyethylene Terephthalates, Protein Conformation, Crystallography, X-Ray, Molecular Dynamics Simulation
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