Cooperation of Two Bifunctional Enzymes in the Biosynthesis and Attachment of Deoxysugars of the Antitumor Antibiotic Mithramycin

Authors

  • Dr. Guojun Wang,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA)
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  • Dr. Pallab Pahari,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA)
    2. Present address: Synthetic Organic Chemistry Division, CSIR North East Institute of Science and Technology, Jorhat, Assam, 785006 (India)
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  • Dr. Madan K. Kharel,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA)
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  • Dr. Jing Chen,

    1. Department of Biochemistry, University of Kentucky, Lexington, KY 40536 (USA)
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  • Prof. Dr. Haining Zhu,

    1. Department of Biochemistry, University of Kentucky, Lexington, KY 40536 (USA)
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  • Prof. Dr. Steven G. Van Lanen,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA)
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  • Prof. Dr. Jürgen Rohr

    Corresponding author
    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA)
    • Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536 (USA)
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  • This work was supported by the NIH grant CA 091901 to J.R.

Abstract

original image

Two bifunctional enzymes cooperate in the assembly and the positioning of two sugars, D-olivose and D-mycarose, of the anticancer antibiotic mithramycin. MtmC finishes the biosynthesis of both sugar building blocks depending on which MtmGIV activity is supported. MtmGIV transfers these two sugars onto two structurally distinct acceptor substrates. The dual function of these enzymes explains two essential but previously unidentified activities.

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