Machine Learning-Supported Enzyme Engineering toward Improved CO₂-Fixation of Glycolyl-CoA Carboxylase.

ABSTRACT: Glycolyl-CoA carboxylase (GCC) is a new-to-nature enzyme that catalyzes the key reaction in the tartronyl-CoA (TaCo) pathway, a synthetic photorespiration bypass that was recently designed to improve photosynthetic CO₂ fixation. GCC was created from propionyl-CoA carboxylase (PCC) through five mutations. However, despite reaching activities of naturally evolved biotin-dependent carboxylases, the quintuple substitution variant GCC M5 still lags behind 4-fold in catalytic efficiency compared to its template PCC and suffers from futile ATP hydrolysis during CO₂ fixation. To further improve upon GCC M5, we developed a machine learning-supported workflow that reduces screening efforts for identifying improved enzymes. Using this workflow, we present two novel GCC variants

SUBMITTER: Marchal DG 

PROVIDER: S-EPMC10729300 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature