Year: 2024
Type: article
Abstract: This article reports on the engineering of phenylalanine ammonialyases (PALs) for the enantioselective synthesis of aspartic acid derivatives via biocatalytic hydroamination of alkenes.PALs typically suffer from a limited substrate scope and demonstrate poor enantioselectivity with electron-deficient substrates.The study employs structure-based engineering of PALs from Planctomyces brasiliensis (PbPAL), identifying the active site residue L205 as critical for enhancing enantioselectivity.The engineered PALs exhibit high α-regioselectivity, enantioselectivity, and a broad substrate range, enabling preparative-scale hydroaminations of previously inaccessible substrates like amide and ester containing fumaric acid derivatives.These advancements were demonstrated by producing tert-butyl protected L-aspartic acid, a key intermediate in peptide synthesis.This work highlights the potential of biocatalysis for synthesizing amino acids under mild conditions with tunable selectivity, extending the industrial applications of C-N lyases and marking a significant step forward in the field.Authors' comments: "We were excited to convert phenylalanine ammonia lyase, traditionally limited to aromatic amino acids, into biocatalysts producing valuable aspartic acid derivatives.Controlling hydroamination enantioselectivity opens new opportunities for this enzyme class."
Institution: University of Zurich
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4403855366