Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model.
Angew Chem Int Ed Engl
; 61(50): e202202711, 2022 12 12.
Article
em En
| MEDLINE
| ID: mdl-36259321
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article