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Engineered L ‐Serine Hydroxymethyltransferase from Streptococcus thermophilus for the Synthesis of α,α‐Dialkyl‐α‐Amino Acids
Author(s) -
Hernandez Karel,
Zelen Igor,
Petrillo Giovanna,
Usón Isabel,
Wandtke Claudia M.,
Bujons Jordi,
Joglar Jesús,
Parella Teodor,
Clapés Pere
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201411484
Subject(s) - serine hydroxymethyltransferase , stereocenter , serine , chemistry , amino acid , stereoselectivity , stereochemistry , aldol reaction , streptococcus thermophilus , enzyme , enantioselective synthesis , biochemistry , catalysis , fermentation , lactobacillus
α,α‐Disubstituted α‐amino acids are central to biotechnological and biomedical chemical processes for their own sake and as substructures of biologically active molecules for diverse biomedical applications. Structurally, these compounds contain a quaternary stereocenter, which is particularly challenging for stereoselective synthesis. The pyridoxal‐5′‐phosphate (PLP)‐dependent L ‐serine hydroxymethyltransferase from Streptococcus thermophilus (SHMT Sth ; EC 2.1.2.1) was engineered to achieve the stereoselective synthesis of a broad structural variety of α,α‐dialkyl‐α‐amino acids. This was accomplished by the formation of quaternary stereocenters through aldol addition of the amino acids D ‐Ala and D ‐Ser to a wide acceptor scope catalyzed by the minimalist SHMT Sth Y55T variant overcoming the limitation of the native enzyme for Gly. The SHMT Sth Y55T variant tolerates aromatic and aliphatic aldehydes as well as hydroxy‐ and nitrogen‐containing aldehydes as acceptors.