Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent Pathway

Research output: Contribution to journalArticle

Abstract

Phenylalanine ammonia lyases (PALs) belong to a family of 4-methylideneimidazole-5-one (MIO) cofactor dependent enzymes which are responsible for the conversion of L-phenylalanine into trans-cinnamic acid in eukaryotic and prokaryotic organisms. Under conditions of high ammonia concentration, this deamination reaction is reversible and hence there is considerable interest in the development of PALs as biocatalysts for the enantioselective synthesis of non-natural amino acids. Herein the discovery of a previously unobserved competing MIO-independent reaction pathway, which proceeds in a non-stereoselective manner and results in the generation of both L- and D-phenylalanine derivatives, is described. The mechanism of the MIO-independent pathway is explored through isotopic-labeling studies and mutagenesis of key active-site residues. The results obtained are consistent with amino acid deamination occurring by a stepwise E1 cB elimination mechanism.

Bibliographical metadata

Original languageEnglish
Pages (from-to)4652-4656
JournalAngewandte Chemie - International Edition
Volume53
Issue number18
DOIs
Publication statusPublished - 25 Apr 2014

Related information

Researchers

View all