Effective engineering of a ketoreductase for the biocatalytic synthesis of an ipatasertib precursor.

ABSTRACT: Semi-rational enzyme engineering is a powerful method to develop industrial biocatalysts. Profiting from advances in molecular biology and bioinformatics, semi-rational approaches can effectively accelerate enzyme engineering campaigns. Here, we present the optimization of a ketoreductase from Sporidiobolus salmonicolor for the chemo-enzymatic synthesis of ipatasertib, a potent protein kinase B inhibitor. Harnessing the power of mutational scanning and structure-guided rational design, we created a 10-amino acid substituted variant exhibiting a 64-fold higher apparent k_cat and improved robustness under process conditions compared to the wild-type enzyme. In addition, the benefit of algorithm-aided enzyme engineering was studied to derive correlations in protein sequence-function

SUBMITTER: Honda Malca S 

PROVIDER: S-EPMC10902378 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature