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Daniel Klein-Marcuschamer, Parayil Kumaran Ajikumar and Gregory Stephanopoulos

Engineering microbial cell factories for biosynthesis of isoprenoid molecules: beyond lycopene. Daniel Klein-Marcuschamer, Parayil Kumaran Ajikumar and Gregory Stephanopoulos. Table of Contents. Introduction Taxol Lycopene, Isoprenoids, Carotenoids Background, Pathway

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Daniel Klein-Marcuschamer, Parayil Kumaran Ajikumar and Gregory Stephanopoulos

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  1. Engineering microbial cell factories for biosynthesis of isoprenoidmolecules: beyond lycopene Daniel Klein-Marcuschamer, Parayil Kumaran Ajikumar and Gregory Stephanopoulos

  2. Table of Contents • Introduction • Taxol • Lycopene, Isoprenoids, Carotenoids • Background, Pathway • Three Problems • Substrate availability • Intermediate build-up • Increase storage capacity • Conclusion

  3. http://www.shipping-worldwide.com/bigstockphoto_Warehouse_2012713.jpghttp://www.shipping-worldwide.com/bigstockphoto_Warehouse_2012713.jpg

  4. Taxol https://upload.wikimedia.org/wikipedia/commons/thumb/5/59/Taxol.svg/1280px-Taxol.svg.png

  5. Taxol

  6. Taxol It’s Complicated

  7. Taxol It’s Complicated = $$$$

  8. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  9. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  10. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  11. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  12. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  13. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  14. Metabolic Engineering:‘de novo engineered microbes’ http://www.earthtimes.org/nsimages/files/genetic_engineering_gm_encyclopaedia.jpg

  15. Metabolic Engineering:‘de novo engineered microbes’ http://rsif.royalsocietypublishing.org/content/10/78/20120671

  16. Metabolic Engineering:‘de novo engineered microbes’ http://rsif.royalsocietypublishing.org/content/10/78/20120671 http://www.rcsb.org/pdb/101/motm.do?momID=152

  17. Metabolic Engineering:‘de novo engineered microbes’ http://rsif.royalsocietypublishing.org/content/10/78/20120671 http://www.brooklyn.cuny.edu/bc/ahp/LAD/C7/graphics/C7_atp_1.GIF http://www.rcsb.org/pdb/101/motm.do?momID=152

  18. ?

  19. Isoprenoids

  20. Isoprenoids x

  21. Isoprenoids x

  22. Isoprenoids x

  23. Isoprenoids http://seniorhousingforum.net/sites/seniorhousingforum.net/files/2014/03/drugsinhand.jpg x http://recipes.saladmaster.com/sites/default/files/styles/large/public/istock_000016591318xsmall_0.jpg?itok=ZrVwUlCW http://www.inkworldmagazine.com/contents/displayImage/29681

  24. Isoprenoids x http://gizmodo.com/5887825/what-are-steroids

  25. Carotenoids 8

  26. Carotenoids 8 Tetraterpenoid

  27. Lycopene http://hookedoniron.com/wp-content/uploads/2011/04/lycopene.jpg

  28. MEP & MVA Pathways Methylerythritol Phosphate Mevalonic Acid

  29. MEP & MVA Pathways Methylerythritol Phosphate Mevalonic Acid IPP & DMAPP Isopentenyl Pyrophosphate Dimethylallyl Diphosphate

  30. MEP & MVA Pathways Methylerythritol Phosphate Mevalonic Acid IPP & DMAPP Isopentenyl Pyrophosphate Dimethylallyl Diphosphate Isoprenoids

  31. The big picture

  32. The big picture

  33. The Three Problems: Ensuring Substrate Availability Balancing Intermediate Pools Improving Storage Capacity for End Products

  34. Ensuring Substrate Availability • Focus on increasing the availability of substrates (IPP, DMAPP, FPP).

  35. Ensuring Substrate Availability • Focus on increasing the availability of substrates (IPP, DMAPP, FPP).

  36. A) Stoichiometric Flux Balance Analysis • A method of modelling a metabolic network to identify enzymes which heavily influence carbon flux. (PT5-idi / PT5-ispDF / PT5-dxs)

  37. A) Stoichiometric Flux Balance Analysis • A method of modelling a metabolic network to identify enzymes which heavily influence carbon flux. (PT5-idi- / PT5-ispDF- / PT5-dxs-)

  38. B) Metabolic Control Structure • Diverts carbon flux to lycopene during the stationary phase of growth. • PT5-idi and PT5-pps under glnAp2.

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