Enzymatic Synthesis of Lipid II and Analogues

Authors

  • Lin-Ya Huang,

    1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
    2. Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
    3. Graduate Institute of Biotechnology, National Chung-Hsing, University, 250 Kuo Kuang Rd., Taichung 402 (Taiwan)
    4. Biotechnology Center, National Chung-Hsing University, 250 Kuo Kuang Rd., Taichung 402 (Taiwan)
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  • Shih-Hsien Huang,

    1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
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  • Ya-Chih Chang,

    1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
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  • Wei-Chieh Cheng,

    1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
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  • Ting-Jen R. Cheng,

    Corresponding author
    1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
    • Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)===

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  • Chi-Huey Wong

    Corresponding author
    1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
    2. Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)
    3. Graduate Institute of Biotechnology, National Chung-Hsing, University, 250 Kuo Kuang Rd., Taichung 402 (Taiwan)
    4. Biotechnology Center, National Chung-Hsing University, 250 Kuo Kuang Rd., Taichung 402 (Taiwan)
    • Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan)===

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  • Financial support from Academia Sinica, Taiwan.

Abstract

The emergence of antibiotic resistance has prompted active research in the development of antibiotics with new modes of action. Among all essential bacterial proteins, transglycosylase polymerizes lipid II into peptidoglycan and is one of the most favorable targets because of its vital role in peptidoglycan synthesis. Described in this study is a practical enzymatic method for the synthesis of lipid II, coupled with cofactor regeneration, to give the product in a 50–70 % yield. This development depends on two key steps: the overexpression of MraY for the synthesis of lipid I and the use of undecaprenol kinase for the preparation of polyprenol phosphates. This method was further applied to the synthesis of lipid II analogues. It was found that MraY and undecaprenol kinase can accept a wide range of lipids containing various lengths and configurations. The activity of lipid II analogues for bacterial transglycolase was also evaluated.

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