Nucleophile Promiscuity of Engineered Class II Pyruvate Aldolase YfaU from E. Coli

Karel Hernández, Jesús Joglar, Jordi Bujons, Teodor Parella, Pere Clapés

    Research output: Contribution to journalArticleResearchpeer-review

    7 Citations (Scopus)

    Abstract

    © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Pyruvate-dependent aldolases exhibit a stringent selectivity for pyruvate, limiting application of their synthetic potential, which is a drawback shared with other existing aldolases. Structure-guided rational protein engineering rendered a 2-keto-3-deoxy-l-rhamnonate aldolase variant, fused with a maltose-binding protein (MBP-YfaU W23V/L216A), capable of efficiently converting larger pyruvate analogues, for example, those with linear and branched aliphatic chains, in aldol addition reactions. Combination of these nucleophiles with N-Cbz-alaninal (Cbz=benzyloxycarbonyl) and N-Cbz-prolinal electrophiles gave access to chiral building blocks, for example, derivatives of (2S,3S,4R)-4-amino-3-hydroxy-2-methylpentanoic acid (68 %, d.r. 90:10) and the enantiomer of dolaproine (33 %, d.r. 94:6) as well as a collection of unprecedented α-amino acid derivatives of the proline and pyrrolizidine type. Conversions varied between 6–93 % and diastereomeric ratios from 50:50 to 95:5 depending on the nucleophilic and electrophilic components.
    Original languageEnglish
    Pages (from-to)3583-3587
    JournalAngewandte Chemie - International Edition
    Volume57
    Issue number14
    DOIs
    Publication statusPublished - 26 Mar 2018

    Keywords

    • aldol reactions
    • amino acids
    • biocatalysis
    • pyruvate aldolases

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