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Opium poppy, Papaver somniferum Alternative products – alternative uses.

Opium poppy, Papaver somniferum Alternative products – alternative uses. Phil Larkin CSIRO, Canberra. Australian poppy industry. >50% of world’s legally traded opiates Demonstrated the power of genetics to transform the industry to new products Thebaine poppies ( top1 mutation)

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Opium poppy, Papaver somniferum Alternative products – alternative uses.

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  1. Opium poppy, Papaver somniferumAlternative products – alternative uses. Phil Larkin CSIRO, Canberra

  2. Australian poppy industry • >50% of world’s legally traded opiates • Demonstrated the power of genetics to transform the industry to new products • Thebaine poppies (top1 mutation) • Thebaine feedstock for high value painkillers, such as buprenorphine, oxycodone.

  3. Top1 mutation CO52 Thebaine Control mutant Zero morphine and codeine. Proprietary mutation of Tasmanian Alkaloids Morphine-pathway block in top1 poppies. Millgate, Pogson, Wilson, Kutchan, Zenk, Gerlach, Fist, Larkin. Nature 431:413-414 (2004)

  4. Transgenic poppies • Biotechnology is another strategy capable of transforming the industry: • Increasing morphinan content • Novel products

  5. Transformation of Poppy Hypocotyl explants Agrobacterium Black primary callus White embryogenic callus Somatic embryos

  6. Metabolic Engineering of Opium Poppy Increasing alkaloid yield Engineering novel products reticuline thebaine hpRNAi morphine morphine anticancer and antimalarial activities analgesics

  7. Transgenic over-expression of COR (codeinone reductase) increases yield • COR gene transcript is increased • Morphinan alkaloid content is increased …..

  8. Cor transgenics GH2002 GH2003 FIELD2003 GH2004

  9. COR over-expression – Field Trial * , P<0.05 **, P<0.01 Control n=18, 20 plants per replicate Transgenics n=6, 20 plants per replicate

  10. Metabolic engineering for alternative products • Zero opium poppy by genetic engineering • CSIRO gene silencing technology to shut down all opiates. • Hairpin RNAi • E.g. Target gene: codeinone reductase • Accumulation of alternative non-opiate product, reticuline.

  11. Opiate-free poppy codeinone reductase

  12. Opiate-free poppy Potential feedstock for other bioactives Allen, RS et al. (2004) RNAi-mediated replacement of morphine with nonnarcotic alkaloid reticuline in opium poppy. Nature Biotechnology22, 1559-66.

  13. Opiate-free poppy Transgenic poppies Control poppies Morphine, codeine and thebaine replaced by reticuline, codamine, laudanine and laudanosine. standards Ls Ln Cm R T O C M

  14. Proposal for Afghan Poppy Industry Phased transformation to a legal non-opiate industry: • Phase 1. Biodiesel from poppy seed oil. • Phase 2. Higher value “soft” biodiesel. • Phase 3. Industrial and pharmaceutical products.

  15. Poppyseed oil for biodiesel. • Current world diesel consumption 1087 billion litres p.a. • Biodiesel currently accounts for 0.4%. • Poppy yields 1.8 tonnes/ha seed (cf. 2.4 for canola) • 45-50% oil content (cf. 40% in canola) • 0.8 tonnes oil per ha. • Afghan poppy area in 2004 was 131,000 ha • <2 % of arable land • Would produce 100,000 tonnes of oil • = 2.5% of current world biodiesel consumption. • Scope to expand production greatly. • Protein “meal” byproduct as food and feed.

  16. Phase 1. Biodiesel from poppy seed oil. • Replacement seed of opiate-free poppies mutation • Mutant cv. Sujata, opiate-free, opium-free poppy (CSIR Lucknow, India) • Village-scale oil press and biodiesel processing • Local energy supply • Transport fuel • Electricity generators • Basis of a carbon-neutral export biodiesel industry. • Low tech and high volume • Requiring minimal adjustment from the poppy growing culture and expertise. • Begins the process of legalising the industry: • Agronomic support • Potential Carbon subsidies • Breeding support • Trade support

  17. Phase 2. Higher value “soft” biodiesel. Value adding to poppy oil with biotechnology • Increased oil yield • Overexpressing DAGAT2 (boost transfer of last acyl to glycerol) • High oleic biodiesel. • Polyunsaturates can form oxidised polymers which reduce engine performance. • High oleic oils (monounsaturates) are preferred. • Well attested CSIRO technology used to produce high oleic oils in soybean, canola, flax and cottonseed oils: • RNAi silencing 12-desaturase (high oleic) • RNAi silencing FATB thioesterase (eliminate palmitic) • High oleic poppy oil also a healthier food oil.

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