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

Carlos J. Moreno, Karel Hernández, Simon J. Charnok, Samantha Gittings, Michael Bolte, Jesús Joglar, Jordi Bujons, Teodor Parella, Pere Clapés*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    20 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)4660-4669
    Number of pages10
    JournalACS catalysis
    Issue number8
    Publication statusPublished - 16 Apr 2021


    • 2-oxoacid aldolase
    • aldol addition
    • biocatalysis
    • reductive amination
    • transaminases
    • γ-hydroxy-α-amino acids


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