Switching Enantioselectivity in Phenylalanine Ammonia Lyase for the Synthesis of Electron-Deficient Aromatic d-Amino Acids.

ABSTRACT: Aromatic d-amino acids (d-AAs) are valuable building blocks in drug discovery and peptide therapeutics, yet their direct and efficient biocatalytic synthesis remains a challenge. Here, we report the rational engineering of phenylalanine ammonia lyase from Planctomyces brasiliensis (PbPAL) to enable asymmetric hydroamination for the enantioselective synthesis of d-aromatic amino acids. By targeting active-site residue L205, we identified variants capable of highly d-enantioselective hydroamination, with L205F enabling the transformation of electron-deficient aryl acrylates with >99% enantiomeric excess (ee). The synthetic utility of this platform was demonstrated by gram-scale synthesis of d-benzoxazole and substituted 2-pyridylalanines. Structural and mutational studies revealed distinct r

SUBMITTER: Buslov I 

PROVIDER: S-EPMC12535398 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature