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Morphine-pathway block in top1 poppies

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This opium poppy mutant provides chemical precursors for non-addictive analgesics.

Abstract

The opium poppy is a source of the pharmaceuticals codeine, morphine and their derived analgesics. Here we describe the initial characterization of the poppy mutant known as top1 (for ‘thebaine oripavine poppy 1’), which accumulates the morphine and codeine precursors thebaine and oripavine and does not complete their biosynthesis into morphine and codeine. The original discovery of top1 stimulated a re-engineering of the opioid industry in the island state of Tasmania, which grows over 40% of the world's licit opiates, in order to produce thebaine and oripavine efficiently from morphine-free poppy crops to provide precursors for highly effective analgesics and for treatment of opioid addiction.

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Figure 1: An abbreviated biosynthesis pathway, leading from tyrosine to morphine and showing the two alternative routes from thebaine to morphine.
Figure 2: High-pressure liquid chromatography traces of alkaloid profiles from the control parent poppy (upper) and the mutant top1 (lower).

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Authors and Affiliations

  1. CSIRO Plant Industry, Black Mountain, Canberra, ACT, 2601, Australia

    Anthony G. Millgate, Iain W. Wilson & Philip J. Larkin

  2. School of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT, 0200, Australia

    Anthony G. Millgate & Barry J. Pogson

  3. Department of Natural Product Biotechnology, Leibniz Institute of Plant Biochemistry, Halle (Saale), 06120, Germany

    Toni M. Kutchan

  4. Biozentrum Universität Halle, Halle (Saale), 06120, Germany

    Meinhart H. Zenk

  5. Johnson & Johnson, Locked Bag 4555, Strawberry Hills, 2012, New South Wales, Australia

    Wayne L. Gerlach

  6. Tasmanian Alkaloids, Westbury, 7303, Tasmania, Australia

    Anthony J. Fist

Authors
  1. Anthony G. Millgate
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  2. Barry J. Pogson
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  3. Iain W. Wilson
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  4. Toni M. Kutchan
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  5. Meinhart H. Zenk
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  6. Wayne L. Gerlach
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  7. Anthony J. Fist
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  8. Philip J. Larkin
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Correspondence to Philip J. Larkin.

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Millgate, A., Pogson, B., Wilson, I. et al. Morphine-pathway block in top1 poppies. Nature 431, 413–414 (2004). https://doi.org/10.1038/431413a

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