Substrate-Specific Evolution of Amine Dehydrogenases for Accessing Structurally Diverse Enantiopure (R)-β-Amino Alcohols

Xinjian Yin, Wenzhong Gong, Yujing Zeng, Hulin Qiu, Lan Liu, Frank Hollmann*, Bishuang Chen*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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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.

Original languageEnglish
Pages (from-to)837-845
Number of pages9
JournalACS Catalysis
Issue number2
Publication statusPublished - 2024


  • amine dehydrogenases
  • biocatalysis
  • enantiopure β-amino alcohols
  • oxidative deamination
  • protein engineering


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