LovG: The Thioesterase Required for Dihydromonacolin L Release and Lovastatin Nonaketide Synthase Turnover in Lovastatin Biosynthesis

Authors

  • Wei Xu,

    1. Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
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  • Dr. Yit-Heng Chooi,

    1. Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
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  • Jin W. Choi,

    1. Department of Chemical Engineering and Material Science, University of California, Irvine, Irvine, CA 92697 (USA)
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  • Prof. Shuang Li,

    1. Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
    2. School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006 (PR China)
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  • Prof. John C. Vederas,

    1. Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 (Canada)
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  • Prof. Nancy A. Da Silva,

    1. Department of Chemical Engineering and Material Science, University of California, Irvine, Irvine, CA 92697 (USA)
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  • Prof. Yi Tang

    Corresponding author
    1. Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
    • Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)

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  • This work was supported by the US National Institutes of Health (1R01GM085128 and 1R01GM092217) to Y.T. Natural Sciences & Engineering Research Council of Canada (NSERC) and Canada Research Chair in Bioorganic & Medicinal Chemistry to J.V. We thank Prof. D. K. Ro for providing the expression plasmid of LovA.

Abstract

original image

No Lov lost: The cryptic thioesterase LovG was found to be responsible for product release from the lovastatin nonaketide synthase (LNKS or LovB; see scheme). LovG also helped improve the turnover of LovB through hydrolysis of incorrectly made intermediates, freeing LovB for another round of catalysis.

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