Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH..
Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Angewandte Chemie (International ed. in English) - 61(2022), 50 vom: 12. Dez., Seite e202202711 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tian, Pengfei [VerfasserIn] |
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| Links: |
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| Themen: |
Coevolution |
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| Anmerkungen: |
Date Completed 07.12.2022 Date Revised 15.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/anie.202202711 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. | ||
| 520 | |a Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Coevolution | |
| 650 | 4 | |a Molecular Dynamics Simulations | |
| 650 | 4 | |a Monte Carlo Simulations | |
| 650 | 4 | |a Potts Models | |
| 650 | 4 | |a Protein Design | |
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| 700 | 1 | |a Lemaire, Adrien |e verfasserin |4 aut | |
| 700 | 1 | |a Sénéchal, Fabien |e verfasserin |4 aut | |
| 700 | 1 | |a Habrylo, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Antonietti, Viviane |e verfasserin |4 aut | |
| 700 | 1 | |a Sonnet, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Lefebvre, Valérie |e verfasserin |4 aut | |
| 700 | 1 | |a Isa Marin, Frederikke |e verfasserin |4 aut | |
| 700 | 1 | |a Best, Robert B |e verfasserin |4 aut | |
| 700 | 1 | |a Pelloux, Jérôme |e verfasserin |4 aut | |
| 700 | 1 | |a Mercadante, Davide |e verfasserin |4 aut | |
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