Print Email Facebook Twitter Substrate-Specific Evolution of Amine Dehydrogenases for Accessing Structurally Diverse Enantiopure (R)-β-Amino Alcohols Title Substrate-Specific Evolution of Amine Dehydrogenases for Accessing Structurally Diverse Enantiopure (R)-β-Amino Alcohols Author Yin, Xinjian (Sun Yat-sen University) Gong, Wenzhong (Sun Yat-sen University) Zeng, Yujing (Sun Yat-sen University) Qiu, Hulin (Sun Yat-sen University) Liu, Lan (Sun Yat-sen University) Hollmann, F. (TU Delft BT/Biocatalysis) Chen, Bishuang (Sun Yat-sen University) Date 2024 Abstract The biocatalytic oxidative deamination of β-amino alcohols holds significant practical potential in kinetic resolution and/or deracemization process to access (R)-β-amino alcohols. This study exemplifies a notable instance of acquisition and utilization of this valuable oxidative deamination activity. Initially, the mutation N261M (M0) was identified to endow a native valine dehydrogenase with oxidative deamination activity toward a few (S)-β-amino alcohols. Subsequently, a phylogenetic analysis-guided, double-code saturation mutagenesis strategy was proposed to engineer M0's side-chain binding site. This strategy facilitated the substrate-specific evolution of M0, resulting in the creation of a panel of mutants (M1-M4) with noteworthy oxidative deamination activity toward structurally diverse (S)-β-amino alcohols. Using these engineered amine dehydrogenases, termed as β-amino alcohol dehydrogenases (β-AADHs), the complete kinetic resolution and even deracemization of a range of β-amino alcohols have been achieved. This work reports distinct biocatalysts and a synthetic strategy for the synthesis of enantiopure (R)-β-amino alcohols and offers an innovative approach for substrate-specificity engineering of enzymes. Subject amine dehydrogenasesbiocatalysisenantiopure β-amino alcoholsoxidative deaminationprotein engineering To reference this document use: http://resolver.tudelft.nl/uuid:edaba1eb-4d33-4957-b21e-f3b66e584c90 DOI https://doi.org/10.1021/acscatal.3c04995 ISSN 2155-5435 Source ACS Catalysis, 14 (2), 837-845 Part of collection Institutional Repository Document type journal article Rights © 2024 Xinjian Yin, Wenzhong Gong, Yujing Zeng, Hulin Qiu, Lan Liu, F. Hollmann, Bishuang Chen Files PDF yin-et-al-2024-substrate- ... re-_r_.pdf 5.17 MB Close viewer /islandora/object/uuid:edaba1eb-4d33-4957-b21e-f3b66e584c90/datastream/OBJ/view