Year: 2022
Type: article
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.
Source: Angewandte Chemie
Institutions: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Biologie des Plantes et Innovation, UMR Transfrontalière BioEcoAgro, Agents infectieux, résistance et chimiothérapie, University of Copenhagen, University of Auckland
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,100
OpenAlex ID: W4306847649