Publicación Artículo científico (article).

Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions

Digital.CSIC. Repositorio Institucional del CSIC
Digital.CSIC. Repositorio Institucional del CSIC
  • Moreno, Carlos J.
  • Hernández Sánchez, Karel
  • Charnock, Simon J.
  • Gittings, Samantha
  • Bolte, Michael
  • Joglar Tamargo, Jesús
  • Bujons, Jordi
  • Parella, Teodor
  • Clapés Saborit, Pere
Three enzymatic routes toward γ-hydroxy-α-amino acids by tandem aldol addition–transamination one-pot two-step reactions are reported. The approaches feature an enantioselective aldol addition of pyruvate to various nonaromatic aldehydes catalyzed by trans-o-hydroxybenzylidene pyruvate hydratase-aldolase (HBPA) from Pseudomonas putida. This affords chiral 4-hydroxy-2-oxo acids, which were subsequently enantioselectively aminated using S-selective transaminases. Three transamination processes were investigated involving different amine donors and transaminases: (i) l-Ala as an amine donor with pyruvate recycling, (ii) a benzylamine donor using benzaldehyde lyase from Pseudomonas fluorescens Biovar I (BAL) to transform the benzaldehyde formed into benzoin, minimizing equilibrium limitations, and (iii) l-Glu as an amine donor with a double cascade comprising branched-chain α-amino acid aminotransferase (BCAT) and aspartate amino transferase (AspAT), both from E. coli, using l-Asp as a substrate to regenerate l-Glu. The γ-hydroxy-α-amino acids thus obtained were transformed into chiral α-amino-γ-butyrolactones, structural motifs found in many biologically active compounds and valuable intermediates for the synthesis of pharmaceutical agents., This project has received funding from the Ministerio de Ciencia e Innovación (MICIN), cofinanced by the Fondo Europeo de Desarrollo Regional (FEDER) (grants RTI2018-094637-B-I00 to P.C. and PGC2018-095808-B-I00 to T.P.), and Programación Conjunta Internacional (PCI2018-092937), through the EU initiative ERA CoBioTech under grant agreement No [722361] to P.C and S.J.Ch.) (Tralaminol)., Peer reviewed

Digital.CSIC. Repositorio Institucional del CSIC

Digital.CSIC. Repositorio Institucional del CSIC
Ver en:
Digital.CSIC. Repositorio Institucional del CSIC