Synthetic biology of avermectin for production improvement and structure diversification

Authors

  • Ying Zhuo,

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

  • Tao Zhang,

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

  • Qi Wang,

    1. Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China
    2. Graduate University of Chinese Academy of Sciences, Beijing, P.R. China
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  • Pablo Cruz-Morales,

    1. Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), Irapuato, Mexico
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  • Buchang Zhang,

    1. Institute of Health Sciences, School of Life Sciences, Anhui University, Hefei, P.R. China
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  • Mei Liu,

    1. Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China
    2. Graduate University of Chinese Academy of Sciences, Beijing, P.R. China
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  • Francisco Barona-Gómez,

    Corresponding author
    1. Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), Irapuato, Mexico
    • Correspondence: Dr. Lixin Zhang, Institute of Microbiology, Chinese Academy of Sciences, Beijing100190, P.R. China; Additional correspondence: Dr. Francisco Barona-Gómez, Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), Cinvestav-IPN, Km 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, CP 36822, Mexico

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  • Lixin Zhang

    Corresponding author
    1. Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China
    • Correspondence: Dr. Lixin Zhang, Institute of Microbiology, Chinese Academy of Sciences, Beijing100190, P.R. China; Additional correspondence: Dr. Francisco Barona-Gómez, Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), Cinvestav-IPN, Km 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, CP 36822, Mexico

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Abstract

Natural products are still key sources of current clinical drugs and innovative therapeutic agents. Since wild-type microorganisms only produce natural products in very small quantities, yields of production strains need to be improved by breaking down the precise genetic and biochemical circuitry. Herein, we use avermectins as an example of production improvement and chemical structure diversification by synthetic biology. Avermectins are macrocyclic lactones produced by Streptomyces avermitilis and are well known and widely used for antiparasitic therapy. Given the importance of this molecule and its derivatives, many efforts and strategies were employed to improve avermectin production and generate new active analogues. This review describes the current status of synthetic strategies successfully applied for developing natural-product-producing strains and discusses future prospects for the application of enhanced avermectin production.

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