• Open Access

Abyssomicins from the South China Sea Deep-Sea Sediment Verrucosispora sp.: Natural Thioether Michael Addition Adducts as Antitubercular Prodrugs

Authors

  • Qian Wang,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    2. Graduate University of Chinese Academy of Sciences, Beijing, 100049 (China)
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    • These authors contributed equally to this work.

  • Assoc. Prof. Fuhang Song,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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    • These authors contributed equally to this work.

  • Dr. Xue Xiao,

    1. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072 (Australia)
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    • These authors contributed equally to this work.

  • Pei Huang,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    2. Graduate University of Chinese Academy of Sciences, Beijing, 100049 (China)
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  • Assoc. Prof. Li Li,

    1. Department of Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050 (China)
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  • Prof. Aaron Monte,

    1. Department of Chemistry and Biochemistry, University of Wisconsin-La Crosse, La Crosse, WI 54601 (USA)
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  • Dr. Wael M. Abdel-Mageed,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    2. Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526 (Egypt)
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  • Dr. Jian Wang,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Hui Guo,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    2. Graduate University of Chinese Academy of Sciences, Beijing, 100049 (China)
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  • Dr. Wenni He,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Feng Xie,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Dr. Huanqin Dai,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Miaomiao Liu,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    2. Graduate University of Chinese Academy of Sciences, Beijing, 100049 (China)
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  • Dr. Caixia Chen,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Hao Xu,

    1. Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303 (USA)
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  • Assoc. Prof. Mei Liu,

    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Dr. Andrew M. Piggott,

    1. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072 (Australia)
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  • Assoc. Prof. Xueting Liu,

    Corresponding author
    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    • Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • Prof. Robert J. Capon,

    Corresponding author
    1. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072 (Australia)
    • Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072 (Australia)
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  • Prof. Lixin Zhang

    Corresponding author
    1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
    • Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190 (China)
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  • This work was supported in part by the National Program on Key Basic Research Project (973 program, 2013CB734000, 2012CB725200, 2012CB721006), the National Natural Science Foundation of China (81102369, 30901849, 30911120483, 81102356, 30973665, 30911120484), the CAS Pillar Program (XDA04074000), the Ministry of Science and Technology of China (2011ZX11102-011-11, 2007DFB31620), Genzyme, a Sanofi company, the Institute for Molecular Bioscience, the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312184, The University of Queensland, and the Australian Research Council (ARC LP0989954). L.Z. is an Awardee of the National Distinguished Young Scholar Program in China. We acknowledge Prof. Hans-Peter Fiedler (Universität Tübingen) for providing a sample of atrop-abyssomicin C for reference.

Abstract

original image

From the deep: The title actinomycete yielded three new abyssomicins J–L. The dimeric thioether J (see scheme) represents a unique example of a masked Michael acceptor with anti-TB properties. Mechanistic insights into the biosynthesis, biomimetic synthesis, stability, and biological mechanism of action of abyssomicins aid our understanding of, and prospects for the development of Michael-acceptor-based drugs.

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