Research Interests

The immense biosynthetic potential of plants as a renewable source of fine chemicals and pharmaceuticals has long been recognized. Recent advances in plant biotechnology, molecular biology, and genomics have created promising new opportunities to advance the use of plants as efficient, environmentally friendly, and renewable chemical factories. However, our ability to exploit the biosynthetic capacity of plants to meet future demands for pharmaceuticals and other fine chemicals is dependent on a detailed understanding of the biosynthesis and regulation of secondary metabolic pathways. Development of metabolic engineering strategies as a means to improve and customize plant secondary metabolite production will require a systematic expansion of our molecular toolbox (i.e., cloned genes) and our biochemical catalogue (i.e., knowledge of how pathways are regulated). Plant biotechnology has unprecedented potential for establishing new Canadian and international industries, for diversifying Canada's agricultural business sector and for solving specific social and agronomic problems.

My research is focused on opium poppy (Papaver somniferum), which has the unique ability to synthesize morphine, codeine, and a variety of other benzylisoquinoline alkaloids of pharmaceutical importance. The global market for licit opium, from which the alkaloids are extracted, is in excess of 160 tons annually. In Canada, codeine is found in a wide variety of over-the-counter and prescription medications including pain-relievers and cough syrups. However, opium poppy produces only low quantities of codeine due to a perceived demethylase activity that converts codeine to morphine. Approximately 95% of the morphine extracted from licit opium is chemically converted to codeine, a more versatile pharmaceutical. The large quantities of morphine produced by the plant is the basis for illicit cultivation of opium poppy in many regions of the world for the synthesis of O,O-diacetylmorphine, or heroin. Illicit production of opium exceeds licit usage by almost tenfold. The social impact of heroine in Canada and around the world is indisputable. Research aimed at metabolic engineering in opium poppy could lead to biological alternatives for reducing the production and trafficking of illicit drugs in Canada and around the world. Moreover, paradigms established through improved knowledge of secondary metabolism in opium poppy could also create opportunities to introduce entire pathways into value-added crops currently important to the Canadian economy.

No fewer than eight genes encoding alkaloid biosynthetic enzymes have been cloned from opium poppy. However, the biosynthesis of morphine and related alkaloids involves many more enzymes. Moreover, much remains to be learned about the control of alkaloid biosynthetic pathways, which are clearly under strict regulation in plants. We approach the study of alkaloid biosynthesis in opium poppy, and related species, from a broad scientific perspective that includes biochemistry, molecular and cell biology, genomics, genetic transformation and metabolic engineering. The discovery of new genes involved in alkaloid formation has been accomplished using traditional protein purification and gene cloning techniques as well as more recent hypothesis-generating strategies, including the establishment of an extensive expressed sequence tag database, microarray analysis, proteomics, and function genomics. Our recent cell biology work, employing immunocytochemical and in situ hybridization techniques, has led to a major breakthrough in understanding the unique sites of alkaloid biosynthesis in opium poppy at both the cellular and subcellular levels. We were the first laboratory to report the transformation of opium poppy and other benzylisoquinoline alkaloid-producing plants, and we are using this technology for our functional genomic and metabolic engineering work. My research program is funded through a Canada Research Chair in Plant Biotechnology, NSERC Discovery and Strategic Grants, and private sector contracts.

 

Courses Taught

Graduate Students

Awards

2007 - Canada Research Chair in Plant Metabolic Processes Biotechnology
2004 - C.D. Nelson Award -Outstanding Young Researcher in Canada
2003 - Celebration of Excellence Award - University of Calgary
2002 - Awarded by the Canadian Society of Plant Physiologists - Celebration of Excellence Award

Selected publications

• Liscombe, D.K., Ziegler, J., Schmidt, J., Ammer, C., and Facchini, P.J. (2009) Isolation of novel N-methyltransferases from three benzylisoquinoline alkaloid-producing species by targeted metabolite and transcript profiling. Plant Journal (in press).
  
• Ziegler, J., Brandt, W., Geißler, R., and Facchini, P.J. (2009) Removal of substrate inhibition and increase in maximal velocity in the short chain dehydrogenase/reductase salutaridine reductase involved in morphine biosynthesis. Journal of Biological Chemistry doi:10.1074/jbc.M109.030957.
  
• Ziegler, J., Facchini, P.J., Geißler, R., Schmidt, J., Ammer, C., Kramell, R., Voigtländer, S., Gesell, A., Pienkny, S., and Brandt, W. (2009) Evolution of morphine biosynthesis in opium poppy. Phytochemistry doi:10.1016/j.phytochem.2009.07.006.  
  
• Lee, E.-J., Shaykhutdinov, R., Park, S.-U., Kim, Y.-K., Yang, T.-J., Vogel, H.J., and Facchini, P.J. (2009) Quality assessment of ginseng by 1H NMR metabolite fingerprint and profile analyses. Journal of Food and Agricultural Chemistry 57, 7513-7522.
  
• Zulak, K.G., Khan, M.F., Alcantara, J., Schreimer D., and Facchini, P.J. (2009) Defense response in opium poppy cell cultures revealed by LC-MS/MS proteomics. Molecular and Cellular Proteomics 8, 86-98.
  
• Jain A., Ziegler, J., Liscombe, D.K., Facchini, P.J., Tucker, P.A. and Panjikar S. (2008) Purification, crystallization and preliminary X-ray diffraction analysis of pavine N-methyltransferase from Thalictrum flavum. Acta Crystallographica Section F: Structural Biology and Crystallization F64, 1066-1069.
  
• Hagel, J.M., Yeung, E.C., and Facchini, P.J. (2008) Got milk? - The secret life of laticifers. Trends in Plant Sciences 13, 631-639.
  
• Hagel, J.M., Weljie, A., Vogel, H.J., and Facchini, P.J. (2008) Quantitative 1H-NMR metabolomics as a biochemical genomics platform to study alkaloid biosynthesis in opium poppy. Plant Physiology 147, 1805-1821.
  
• Hagel, J. and Facchini, P.J. (2008) Plant metabolomics: Analytical platforms and integration with functional genomics. Phytochemistry Reviews 7, 479-497.
  
• Facchini, P.J. and De Luca, V. (2008) Opium poppy and Madagascar periwinkle as model non-model sytems to investigate alkaloid biosynthesis in plants. Plant Journal 54, 763-784.
  
• Liscombe, D.K. and Facchini, P.J. (2008) Evolutionary and Cellular Webs in Benzylisoquinoline Alkaloid Biosynthesis. Current Opinion in Biotechnology 19, 173-180.
  
• Zulak, K.G., Weljie, A., Vogel, H.J., and Facchini, P.J. (2008) Quantitative 1H-NMR metabolomics reveals extensive reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures. BMC Plant Biology 8, 5.
  
• Facchini, P.J., Loukanina, N., and Blanche, V. (2008) Genetic transformation via somatic embryogenesis to establish herbicide-resistant opium poppy. Plant Cell Reports 27, 719-727.
  
• Ziegler, J. and Facchini, P.J. (2008) Alkaloid biosynthesis: metabolism and trafficking. Annual Review of Plant Biology 59, 735-769.
  
• Berkner, H., Engelhorn, J., Liscombe, D.K., Schweimer K., Wöhrl, B.M., Facchini, P.J., Rösch P., and Matecko, I. (2007) Spectroscopic analysis and molecular modeling suggest norcoclaurine synthase is a true member of the PR10-protein family. Protein Expression and Purification 56, 197-204.
  
• Luk, L.Y.P., Bunn, S., Liscombe, D.K., Facchini, P.J., and Tanner, M. (2007) Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis: an enzymatic Pictet-Spengler reaction. Biochemistry 46, 10153-10161.
  
• Liscombe, D.K. and Facchini, P.J. (2007) Molecular cloning and characterization of tetrahydroprotoberberine cis-N-methyltransferase, an enzyme involved in alkaloid biosynthesis in opium poppy. Journal of Biological Chemistry 282, 14741-14751.
  
• Zulak, K.G., Cornish, A., Daskalchuk, T., Deyholos, M., Goodenowe, D., Gordon, P., Klassen, D., Pelcher, L., Sensen, C., and Facchini, P.J. (2007) Gene transcript and metabolite profiling of elicitor-induced opium poppy cell cultures reveals the coordinate regulation of primary and secondary metabolism. Planta 225, 1085-1106.
  
• Samanani, N., Alcantara, J., Bourgault, R., Zulak, K.G., and Facchini, P.J. (2006) Role of sieve elements and laticifers in the biosynthesis and accumulation of alkaloids in opium poppy. Plant Journal 47, 547-564.