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Angew Chem Int Ed Engl. 2015 Mar 2;54(10):3013-7. doi: 10.1002/anie.201411484. Epub 2015 Jan 21.

Engineered L-serine hydroxymethyltransferase from Streptococcus thermophilus for the synthesis of α,α-dialkyl-α-amino acids.

Author information

1
Dept Química Biológica y Modelización Molecular, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona (Spain).

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.

KEYWORDS:

CC bond formation; aldol reaction; amino acids; enzyme catalysis; quaternary stereocenters

PMID:
25611820
DOI:
10.1002/anie.201411484
[Indexed for MEDLINE]

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