Reshaping the Substrate Binding Pocket of β-Amino Acid Dehydrogenase for the Synthesis of Aromatic β-Amino Acids

Org Lett. 2023 Dec 1;25(47):8469-8473. doi: 10.1021/acs.orglett.3c03366. Epub 2023 Nov 16.

Abstract

By reshaping the substrate-binding pocket of β-amino acid dehydrogenase (β-AADH), some variants were obtained with up to 2560-fold enhanced activity toward the model substrates (S)-β-homophenylalanine and (R)-β-phenylalanine. A few aromatic β-amino acids were prepared with >99% ee and high isolated yields via either kinetic resolution of racemates or reductive amination of the corresponding β-keto acids. This work expands the catalytic capability of β-AADHs and highlights their practical application in the synthesis of pharmaceutically relevant β-amino acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Amino Acid Oxidoreductases* / chemistry
  • Amino Acid Oxidoreductases* / metabolism
  • Amino Acids / metabolism
  • Amino Acids, Aromatic* / metabolism
  • Keto Acids
  • Substrate Specificity

Substances

  • Amino Acids, Aromatic
  • Amino Acid Oxidoreductases
  • Amino Acids
  • Keto Acids