University of Calgary

Peter James Facchini

  • Professor
  • Biochemistry

Awards

2002 – Canada Research Chair in Plant Metabolic Processes Biotechnology

2003 – Celebration of Excellence – University of Calgary

2004 – C.D. Nelson Award – Outstanding Young Plant Biologist in Canada

 

Research Interests

Our research is aimed at understanding the biochemistry, cellular biology, and molecular physiology of plant specialized metabolism with a focus on benzylisoquinoline alkaloid biosynthesis in opium poppy, which remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives. The availability of an extensive toolbox of benzylisoquinoline alkaloid biosynthetic genes, including those encoding the core pathways leading to morphine and noscapine, has created exciting metabolic engineering opportunities in plants and microorganisms. We are also exploring similar interests in the biosynthesis of ephedrine and pseudoephedrine in Ephedra sinica, and other specialized metabolites in a variety of plants.

 

Research Associates

Name

Degree

 

Dr. Jillian Hagel

Dr. Limei Chang

Dr. Xue Chen

Dr. Lisa Yu

Dr. Rongji Chen

Dr. Mehran Dastmalchi

 

PhD

PhD

PhD

PhD

PhD

PhD

 

 

 

 

 

 

PostDoctoral Fellows

Name

Degree

 

Dr. Aparna Singh

Dr. Sukanya Ramasamy

 

PhD

PhD

 

 

 

Graduate Students

Name

Degree program

 

Jeremy Morris

Ivette Menendez

PhD

PhD

 

 

 

Selected Recent Publications

Google Scholar Link

  • Morris, J.S., Groves, R.A., Hagel, J.M., Facchini, P.J. (2018) An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enabes microbial phenylalkylamine production. Journal of Biological Chemistry doi:10.1074/jbc.RA118.004067
  • Chen, X., Hagel, J.M., Chang, L., Tucker, J.E., Shiigi, S.A., Yelpaala, Y., Chen, H.Y., Estrada, R., Colbeck, J., Enquist-Newman, M., Ibàñez, A.B., Cottarel, G., Vidanes, G.M., Facchini, P.J. (2018) A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis. Nature Chemical Biology 14, 738-743.
  • Dastmalchi, M., Chang, L., Torres, M.A., Ng, K.K.S., Facchini, P.J. (2018) Codeine reductase isoforms with differential stability, efficiency and product selectivity in opium poppy. Plant Journal 95, 631-647.
  • Park, M.R., Chen, X., Lang, D.E., Ng, K.K.S., Facchini, P.J. (2018) Heterodimeric O-methyltransferases involved in the biosynthesis of noscapine in opium poppy. Plant Journal 95, 252-267.
  • Hagel, J.M., Facchini, P.J. (2018) Expanding the roles for 2-oxoglutarate-dependent dioxygenases in plant metabolism. Natural Products Reports 35, 721-734.
  • Dastmalchi, M., Park, M.R., Morris, J.S., Facchini, P.J. (2017) Family protraits: The enzymes behind benzylisoquinoline alkaloid diversity. Phytochemistry Reviews 17, 249-277.
  • Hagel, J.M., Facchini, P.J. (2017) Tying the knot: occurrence and possible significance of gene fusions in plant metabolism and beyond. Journal of Experimental Botany 68, 4029-4043.
  • Li, J., Lee, E.-J., Chang, L., Facchini, P.J. (2016) Genes encoding norcoclaurine synthase occur as tandem fusions in the Papaveraceae. Scientific Reports 6, 39256.
  • Dastmalchi, M., Facchini, P.J. (2016) Plant metabolons assembled on demand. Science 354, 829-830.
  • Morris, J.S., Facchini, P.J. (2016) Isolation and characterization of reticuline N-methyltransferase involved in biosynthesis of the aporphine alkaloid magnoflorine in opium poppy. Journal of Biological Chemistry 291, 23416-23427.
  • Torres, M.A., Hoffarth, E., Eugenio, L., Savtchouk, J., Chen, X., Morris, J.S., Facchini, P.J, Ng, K.K.S. (2016) Structural and functional studies of pavine N-methyltransferase from Thalictrum flavum reveal novel insights into substrate recognition and catalytic mechanism. Journal of Biological Chemistry 291, 23403-23415.
  • Morris, J.S., Dastmalchi, M., Li, J., Chang, L., Chen, X., Hagel, J.M., Facchini, P.J. (2016) Plug-and-play benzylisoquinoline alkaloid biosynthetic gene discovery in engineered yeast. Methods in Enzymology 575, 143-178.
  • Kilpatrick, K., Agnieszka, P., Hagel, J., Sumarah, M., Lewinshon, E., Facchini, P.J., Marsolais, F. (2016) Characterization of aromatic aminotransferases from Ephedra sinica Stapf. Amino Acids 48, 1209-1220.
  • Hagel, J.M., Mandal, R., Han, B., Han, J., Dinsmore, D.R., Borchers, C., Wishart, D.S., Facchini, P.J. (2015) Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants. BMC Plant Biology 15, 220
  • Hagel, J.M., Morris, J.S., Lee, E.J.,  Isabel Desgagné-Penix, I., Bross, C.D., Chang, L., Chen, X., Farrow, S.C., Zhang, Y., Soh, J., Sensen. C.W., Facchini, P.J. (2015) Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants. BMC Plant Biology 15, 227
  • Chang, L., Hagel, J.M., Facchini, P.J. (2015) Isolation and characterization of O-methyltransferases involved in the biosynthesis of glaucine in Glaucium flavum. Plant Physiology 169, 1127-1140
  • Farrow, S.C., Facchini, P.J. (2015) Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe2+-dependent dioxygenase from opium poppy. FEBS Letters 589, 2701-2706
  • Farrow, S.C., Hagel, J.M., Beaudoin, G.A.W., Burns D.C., Facchini, P.J. (2015) Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy. Nature Chemical Biology 11, 728-732.
  • Groves, R.A, Hagel, J.M., Zhang, Y., Kilpatrick, K., Levy, A.E., Marsolais, F., Lewissohn, E., Sensen, C.W., Facchini, P.J. (2015) Transcriptome profiling of khat (Catha edulis) and Ephedra sinica reveals gene candidates potentially involved in amphetamine-type alkaloid biosynthesis. PLOS ONE 10, e0119701.
  • Chen, X., Dang, T.T.T., Facchini, P.J. (2015) Noscapine comes of age. Phytochemistry 111, 7-13.
  • Dang, T.T.T., Chen, X., Facchini, P.J. (2015) Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nature Chemical Biology 11, 104-106.
  • Farrow, S.C., Facchini, P.J. (2014) Functional diversity of 2-oxoglutarate/Fe(II)-dependent dioxygenases in plant metabolism. Frontiers in Plant Science 5, 524.
  • Beaudoin, G.A.W., Facchini, P.J. (2014) Alkaloid biosynthesis in opium poppy. Planta 240, 19-32.
  • Fossati, E., Ekins, A., Narcross, L., Zhu, Y., Falgueyret, J.-P., Beaudoin, G., Facchini, P.J., Martin, V.J.J. (2014) Reconstitution of the plant benzylisoquinoline alkaloid dihydrosanguinarine pathway in Saccharomyces cerevisiae. Nature Communications 5, 3283.
  • Dang. T.T.T., Facchini, P.J. (2014) Characterization of N-methylcanadine 1-hydroxylase, a cytochrome P450 catalyzing the first committed step of noscapine biosynthesis in opium poppy. Journal of Biological Chemistry 289, 2013-2026.
  • Dang, T.T.T., Facchini, P.J. (2014) Characterization of canadine synthase, a cytochrome P450 involved in noscapine biosynthesis, from opium poppy. FEBS Letters 588, 198-204.
  • Chen, X., Facchini, P.J. (2014) Short-chain dehydrogenase/reductase catalyzing the final step of noscapine biosynthesis is localized to laticifers in opium poppy. Plant Journal 77, 173-184.
  • Onoyovwe, A., Hagel, J.M., Chen, X., Khan, M.F., Schriemer, D., Facchini, P.J. (2013) Morphine biosynthesis in opium poppy involves an  interplay between two cell types, sieve elements and laticifers. Plant Cell 25, 4110-4122.
  • Farrow, S.C. Facchini, P.J. (2013) Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in protopine and protoberberine alkaloid metabolism in opium poppy. Journal of Biological Chemistry 288, 28997-29012.
  • Lee, E.-J., Hagel, J., Facchini, P.J. (2013) Role of the phloem in the biochemistry and ecophysiology of benzylisoquinoline alkaloid metabolism. Frontiers in Plant Physiology 4, 182.
  • Xiao, M., Zhang, Y., Lee, E.-J., Chen, X., Barber, C.J.S., Chakrabarty, R., Desgagné-Penix, I., Haslam, T.M., Kim, Y.-B., Liu, E., Masada-Atsumi, S., MacNevin, G., Reed, D.W., Stout, J.M., Zerbe, P., Zhang, Y., Bohlmann, J., Covello, P.S., De Luca, V., Page, J.E., Ro, D.-K., Martin, V.J.J., Facchini, P.F., Sensen, C.W. (2013) Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest. Journal of Biotechnology 166, 122-134.
  • Hagel, J.M., Facchini, P.J. (2013) Biochemical genomics to investigate benzylisoquinoline alkaloid biosynthesis in opium poppy and related plants. Plant Cell Physiology 54, 647-672.
  • Beaudoin, G.A.W., Facchini, P.J. (2013) Isolation and characterization of a cDNA encoding (S)-cis-N-methylstylopine 14-hydroxylase from opium poppy, a key enzyme in sanguinarine biosynthesis. Biochemical and Biophysical Research Communications 431, 597-603.
  • Hagel, J.M., Beaudoin, G., Fossati E., Ekins, A., Martin, V.J.J., Facchini, P.J. (2012) Characterization of a flavoprotein oxidase from opium poppy catalyzing the final steps in sanguinarine and papaverine biosynthesis. Journal of Biological Chemistry 287, 42972-42983.
  • Desgagné-Penix, I., Facchini, P.J. (2012) Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy. Plant Journal 72, 331-344.
  • Krizevski, R., Bar, E., Shalit, O., Levi, A., Hagel, J.M., Kilpatrick, K., Marsolais, F., Facchini, P.J., Ben-Shabat, S., Sitrit, Y., Lewinsohn, E. (2012) Benzaldehyde is a precursor of phenylpropylamino alkaloids as revealed by targeted metabolic profiling and comparative biochemical analyses of Ephedra spp. Phytochemistry 81, 71-79.
  • Dang, T.T.T., Onoyovwe, A., Farrow, S.C., Facchini, P.J. (2012) Functional biochemical genomics as a gene discovery platform in benzylisoquinoline alkaloid biosynthesis. Methods in Enzymology 515, 231-266.
  • Hagel, J.M., Krizevski, R., Marsolais, F., Lewinsohn, E., Facchini, P.J.(2012) Biosynthesis of amphetamine analogues in plants. Trends in Plant Science 17, 404-412.
  • Dang, T.T.T., Facchini, P.J. (2012) Characterization of three O-methyltransferases involved in noscapine biosynthesis in opium poppy. Plant Physiology 159, 618-631.
  • Desgagné-Penix, I., Farrow, S.C., Cram, D., Nowak, J., Facchini, P.J. (2012) Integration of deep transcript and targeted metabolite profiles for eight cultivars of opium poppy. Plant Molecular Biology 79, 295-313.
  • Farrow, S.C., Hagel, J.M., Facchini, P.J. (2012) Integration of transcript and metabolite profiling in cell cultures of eighteen plant species from four families that produce benzylisoquinoline alkaloids. Phytochemistry 77, 79-88.
  • Wijekoon, C., Facchini, P.J. (2012) Systematic knockdown of morphine biosynthesis in opium poppy using virus-induced gene silencinng. Plant Journal 69, 1052–1063.
  • Facchini, P.J., Bohlmann, J., Ro, D.K., Page, J.E., Covello, P.S., De Luca, V., Mahadevan, K., Sensen, C.W., Storms, R., Martin, V.J.J. (2012) Synthetic biosystems for the production of high-value plant metabolites. Trends in Biotechnology 30, 127-131.
  • Lee, E.-J., Facchini, P.J. (2011) Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynethsis in opium poppy. Plant Physiology 157, 1067–1078.
  • Lee, E.-J., Facchini, P.J. (2010) Norcoclaurine synthase, a novel enzyme catalyzing the first step in benzylisoquinoline alkaloid biosynthesis, is a member of the PR10 protein family. Plant Cell 22, 3489-3503.
  • Desgagne-Penix, I., Khan, M.F., Sharpe, A., Cram, D., Nowak, J., Schreimer D., Facchini, P.J. (2010) Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures. BMC Plant Biology 10, 252.
  • Hagel, J.M., Facchini, P.J. (2010) Biochemistry and occurrence of O-demethylation in plant metabolism. Frontiers in Plant Physiology 1 (14), 1-7.
  • Hagel, J.M., Facchini, P.J. (2010) Dioxygenases catalyze the O-demthylation steps of morphine biosynthesis in opium poppy. Nature Chemical Biology 6, 273-275.
  • Liscombe, D.K., Ziegler, J., Schmidt, J., Ammer, C., Facchini, P.J. (2009) Isolation of novel N-methyltransferases from three benzylisoquinoline alkaloid-producing species by targeted metabolite and transcript profiling. Plant Journal 60, 729–743
  • Ziegler, J., Brandt, W., Geißler, R., 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 284, 26758–26767.
  • Lee, E.-J., Shaykhutdinov, R., Park, S.-U., Kim, Y.-K., Yang, T.-J., Vogel, H.J., 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., 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., 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., 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., 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.M., Facchini, P.J. (2008) Plant metabolomics: Analytical platforms and integration with functional genomics. Phytochemistry Reviews 7, 479-497.
  • Facchini, P.J., 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., 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., 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., Blanche, V. (2008) Genetic transformation via somatic embryogenesis to establish herbicide-resistant opium poppy. Plant Cell Reports 27, 719-727.
  • Ziegler, J., 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., Tanner, M. (2007) Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis: an enzymatic Pictet-Spengler reaction. Biochemistry 46, 10153-10161
  • Liscombe, D.K., 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., 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.

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