Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations
The PETase enzyme from the bacterium Ideonella sakaiensis can degrade polyethylene terephthalate (PET) back into its polymeric constituents at room temperature, making it an ecologically friendly tool for reducing PET pollution. Computational enzyme optimization is a fundamental tool to accelerate e...
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| Format: | ARTÍCULO |
| Language: | es_ES |
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2024
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| Online Access: | http://dspace.ucuenca.edu.ec/handle/123456789/44084 https://www.scopus.com/record/display.uri?eid=2-s2.0-85178288708&origin=resultslist&sort=plf-f&src=s&sid=29c0f40fe00edee53902660210b03abe&sot=b&sdt=b&s=TITLE-ABS-KEY%28Rate-enhancing+PETase+mutations+determined+through+DFT%2FMM+molecular+dynamics+simulations%29&sl=103&sessionSearchId=29c0f40fe00edee53902660210b03abe&relpos=0 |
| _version_ | 1793400621506756608 |
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| author | Jerves Vazquez, Fanny Carola |
| author_facet | Jerves Vazquez, Fanny Carola |
| author_sort | Jerves Vazquez, Fanny Carola |
| collection | DSpace |
| description | The PETase enzyme from the bacterium Ideonella sakaiensis can degrade polyethylene terephthalate (PET) back into its polymeric constituents at room temperature, making it an ecologically friendly tool for reducing PET pollution. Computational enzyme optimization is a fundamental tool to accelerate enzyme engineering towards the “green revolution” promised by the introduction of enzymatic catalysis in industry. The Asp83Asn mutant generates a sub-optimal reactive conformation that the mutation-induced transition state stabilization does not compensate for, and the barrier is raised by 1.9 kcal mol−1. In contrast, the Asp89Asn mutant keeps a perfect reactive conformation, and the mutation stabilizes the transition state more than the reactants, lowering the barrier by 4.7 kcal mol−1. We show that computer-based well-chosen single-residue substitutions in PETase can decrease the activation barrier significantly, facilitating the development of highly-efficient PETase mutants. The results of this work encourage future studies that aim for rational enzyme engineering on PETase and other enzymes. |
| format | ARTÍCULO |
| id | oai:dspace.ucuenca.edu.ec:123456789-44084 |
| institution | Universidad de Cuenca |
| language | es_ES |
| publishDate | 2024 |
| record_format | dspace |
| spelling | oai:dspace.ucuenca.edu.ec:123456789-440842024-03-05T20:05:37Z Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations Jerves Vazquez, Fanny Carola Optimisations Dynamics simulation Enzymatic catalysis Enzyme engineering Fundamental tools Green revolution Induced transitions Polymeric constituents Reactive conformation Transition state stabilization The PETase enzyme from the bacterium Ideonella sakaiensis can degrade polyethylene terephthalate (PET) back into its polymeric constituents at room temperature, making it an ecologically friendly tool for reducing PET pollution. Computational enzyme optimization is a fundamental tool to accelerate enzyme engineering towards the “green revolution” promised by the introduction of enzymatic catalysis in industry. The Asp83Asn mutant generates a sub-optimal reactive conformation that the mutation-induced transition state stabilization does not compensate for, and the barrier is raised by 1.9 kcal mol−1. In contrast, the Asp89Asn mutant keeps a perfect reactive conformation, and the mutation stabilizes the transition state more than the reactants, lowering the barrier by 4.7 kcal mol−1. We show that computer-based well-chosen single-residue substitutions in PETase can decrease the activation barrier significantly, facilitating the development of highly-efficient PETase mutants. The results of this work encourage future studies that aim for rational enzyme engineering on PETase and other enzymes. 2024-03-05T20:05:34Z 2024-03-05T20:05:34Z 2023 ARTÍCULO 11440546 http://dspace.ucuenca.edu.ec/handle/123456789/44084 https://www.scopus.com/record/display.uri?eid=2-s2.0-85178288708&origin=resultslist&sort=plf-f&src=s&sid=29c0f40fe00edee53902660210b03abe&sot=b&sdt=b&s=TITLE-ABS-KEY%28Rate-enhancing+PETase+mutations+determined+through+DFT%2FMM+molecular+dynamics+simulations%29&sl=103&sessionSearchId=29c0f40fe00edee53902660210b03abe&relpos=0 10.1039/d3nj04204a es_ES application/pdf New Journal of Chemistry |
| spellingShingle | Optimisations Dynamics simulation Enzymatic catalysis Enzyme engineering Fundamental tools Green revolution Induced transitions Polymeric constituents Reactive conformation Transition state stabilization Jerves Vazquez, Fanny Carola Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations |
| title | Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations |
| title_full | Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations |
| title_fullStr | Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations |
| title_full_unstemmed | Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations |
| title_short | Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations |
| title_sort | rate-enhancing petase mutations determined through dft/mm molecular dynamics simulations |
| topic | Optimisations Dynamics simulation Enzymatic catalysis Enzyme engineering Fundamental tools Green revolution Induced transitions Polymeric constituents Reactive conformation Transition state stabilization |
| url | http://dspace.ucuenca.edu.ec/handle/123456789/44084 https://www.scopus.com/record/display.uri?eid=2-s2.0-85178288708&origin=resultslist&sort=plf-f&src=s&sid=29c0f40fe00edee53902660210b03abe&sot=b&sdt=b&s=TITLE-ABS-KEY%28Rate-enhancing+PETase+mutations+determined+through+DFT%2FMM+molecular+dynamics+simulations%29&sl=103&sessionSearchId=29c0f40fe00edee53902660210b03abe&relpos=0 |
| work_keys_str_mv | AT jervesvazquezfannycarola rateenhancingpetasemutationsdeterminedthroughdftmmmoleculardynamicssimulations |