Serine Hydroxymethyl Transferase from Streptococcus thermophilus and L-Threonine Aldolase from Escherichia coli as Stereocomplementary Biocatalysts for the Synthesis of β-Hydroxy-α,ω-diamino Acid Derivatives

Authors

  • Mariana L. Gutierrez,

    1. Biotransformation group. Instituto de Investigaciones Químicas y Ambientales de Barcelona-CSIC. Jordi Girona 18–26, 08034 Barcelona, Spain, Fax: (+34) 9320-4590-4
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  • Xavier Garrabou,

    1. Biotransformation group. Instituto de Investigaciones Químicas y Ambientales de Barcelona-CSIC. Jordi Girona 18–26, 08034 Barcelona, Spain, Fax: (+34) 9320-4590-4
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  • Eleonora Agosta Dr.,

    1. On leave from the Dipartimento di Chimica, Materiali, Ingegneria Chimica “G. Natta”, Politecnico di Milano, Milan, Spain
    2. Present address: Innovex. via Roma 108, 20060 Cassina de' Pecchi, Milano, Italy
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  • Stefano Servi Prof.,

    1. Dipartimento di Chimica, Materiali, Ingegneria Chimica “G. Natta”, Politecnico di Milano, Milan, Italy
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  • Teodor Parella Dr.,

    1. Servei de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, Bellaterra, Spain
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  • Jesús Joglar Dr.,

    1. Biotransformation group. Instituto de Investigaciones Químicas y Ambientales de Barcelona-CSIC. Jordi Girona 18–26, 08034 Barcelona, Spain, Fax: (+34) 9320-4590-4
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  • Pere Clapés Dr.

    1. Biotransformation group. Instituto de Investigaciones Químicas y Ambientales de Barcelona-CSIC. Jordi Girona 18–26, 08034 Barcelona, Spain, Fax: (+34) 9320-4590-4
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Abstract

A novel serine hydroxymethyl transferase from Streptococcus thermophilus (SHMT) and a L-threonine aldolase from Escherichia coli (LTA) were used as stereocomplementary biocatalysts for the aldol addition of glycine to N-Cbz amino aldehydes and benzyloxyacetaldehyde (Cbz=benzyloxycarbonyl). Both threonine aldolases were classified as low-specific L-allo-threonine aldolases, and by manipulating reaction parameters, such as temperature, glycine concentration, and reaction media, SHMT yielded exclusively L-erythro diastereomers in 34–60 % conversion, whereas LTA gave L-threo diastereomers in 30:70 to 16:84 diastereomeric ratios and with 40–68 % conversion to product. SHMT is among the most stereoselective L-threonine aldolases described. This is due, among other things, to its activity–temperature dependence: at 4 °C SHMT has high synthetic activity but negligible retroaldol activity on L-threonine. Thus, the kinetic L-erythro isomer was largely favored and the reactions were virtually irreversible, highly stereoselective, and in turn, gave excellent conversion. It was also found that treatment of the prepared N-Cbz-γ-amino-β-hydroxy-α-amino acid derivatives with potassium hydroxide (1 m) resulted in the spontaneous formation of 2-oxazolidinone derivatives of the β-hydroxyl and γ-amino groups in quantitative yield. This reaction might be useful for further chemical manipulations of the products.

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