title: Engineered L-serine hydroxymethyltransferase from Streptococcus thermophilus for the synthesis of α,α-dialkyl-α-amino acids.
abstract: 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.
authors.affiliation: Dept Química Biológica y Modelización Molecular, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona (Spain).
authors.forename: Karel
authors.initials: K
authors.lastname: Hernandez
authors.forename: Igor
authors.initials: I
authors.lastname: Zelen
authors.forename: Giovanna
authors.initials: G
authors.lastname: Petrillo
authors.forename: Isabel
authors.initials: I
authors.lastname: Usón
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Wandtke
authors.forename: Jordi
authors.initials: J
authors.lastname: Bujons
authors.forename: Jesús
authors.initials: J
authors.lastname: Joglar
authors.forename: Teodor
authors.initials: T
authors.lastname: Parella
authors.forename: Pere
authors.initials: P
authors.lastname: Clapés
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis*; D012696:Glycine Hydroxymethyltransferase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015202:Protein Engineering; D048249:Streptococcus thermophilus / Q000201:enzymology*; D014961:X-Ray Diffraction
chemical_list: D000596:Amino Acids; D012696:Glycine Hydroxymethyltransferase
keywords: CC bond formation; aldol reaction; amino acids; enzyme catalysis; quaternary stereocenters