Premium
Tailored Mutants of Phenylalanine Ammonia‐Lyase from Petroselinum crispum for the Synthesis of Bulky l ‐ and d ‐Arylalanines
Author(s) -
Filip Alina,
Nagy Emma Z. A.,
Tork Souad D.,
Bánóczi Gergely,
Toşa Monica I.,
Irimie Florin D.,
Poppe László,
Paizs Csaba,
Bencze László C.
Publication year - 2018
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201800258
Subject(s) - chemistry , phenylalanine ammonia lyase , phenylalanine , ammonia , mutant , stereochemistry , biphenyl , substrate (aquarium) , biochemistry , organic chemistry , amino acid , biology , ecology , gene
Tailored mutants of phenylalanine ammonia‐lyase from Petroselinum crispum ( Pc PAL) were created and tested in ammonia elimination from various sterically demanding, non‐natural analogues of phenylalanine and in ammonia addition reactions into the corresponding ( E )‐arylacrylates. The wild‐type Pc PAL was inert or exhibited quite poor conversions in both reactions with all members of the substrate panel. Appropriate single mutations of residue F137 and the highly conserved residue I460 resulted in Pc PAL variants that were active in ammonia elimination but still had a poor activity in ammonia addition onto bulky substrates. However, combined mutations that involve I460 besides the well‐studied F137 led to mutants that exhibited activity in ammonia addition as well. The synergistic multiple mutations resulted in substantial substrate scope extension of Pc PAL and opened up new biocatalytic routes for the synthesis of both enantiomers of valuable phenylalanine analogues, such as (4‐methoxyphenyl)‐, (napthalen‐2‐yl)‐, ([1,1′‐biphenyl]‐4‐yl)‐, (4′‐fluoro‐[1,1′‐biphenyl]‐4‐yl)‐, and (5‐phenylthiophene‐2‐yl)alanines.