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

Karel Hernandez, Igor Zelen, Giovanna Petrillo, Isabel Usón, Claudia M. Wandtke, Jordi Bujons, Jesffls Joglar, Teodor Parella, Pere Clapés

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    24 Citations (Scopus)

    Abstract

    © 2015 Wiley-VCH Verlag GmbH & Co. KGaA. α,α-Disubstituted a-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 (SHMTSth; 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 SHMTSth Y55T variant overcoming the limitation of the native enzyme for Gly. The SHMTSth Y55T variant tolerates aromatic and aliphatic aldehydes as well as hydroxy- and nitrogen-containing aldehydes as acceptors.
    Original languageEnglish
    Pages (from-to)3013-3017
    JournalAngewandte Chemie - International Edition
    Volume54
    Issue number10
    DOIs
    Publication statusPublished - 2 Mar 2015

    Keywords

    • Aldol reaction
    • Amino acids
    • C-C bond formation
    • Enzyme catalysis
    • Quaternary stereocenters

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