Dr. Peter James Facchini

More Information

Selected Publications

• Carr, S.C., Rehman, F., Hagel, J.M., Chen, X., Ng, K.K.S., Facchini, P.J. (2024) Two ubiquitous aldo-keto reductases in the genus Papaver support a patchwork model for morphine pathway evolution. Communications Biology 7,1410
• Li, G., Facchini, P.J. (2024) New frontiers in the biosynthesis of psychoactive specialized metabolites. Current Opinion in Plant Biology 83, 102626
• Carr, S.C., Facchini, P.J., Ng, K.K.S. (2024) Structural analysis of a ligand-triggered intermolecular disulfide switch in a major latex protein from opium poppy. Acta Crystallographica D 80, 675-685
• Raithatha, S.A., Hagel, J.M., Matinkhoo, K., Yu, L., Press, D., Cook, S.G., Sharma, G., Dhananjaya D., Jensen, G., Lee, J.B., Cai, C., Gallant, J., Bains, J.S., Tucker, J.E., Facchini, P.J. (2023) Novel psilocybin progrugs with altered pharmacological properties as candidate therapies for treatment-resistant anxiety disorders. Journal of Medicinal Chemistry 67, 1024-1043
• Chen, X., Li, J., Yu, L., Maule, F., Gallant, J., Press, D.J., Raithatha, S., Hagel, J.M., Facchini, P.J. (2023) A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines. Journal of Biological Chemistry 199, 105231
• Watkins, J.L., Li, Q., Yeaman, S., Facchini, P.J. (2023) Elucidation of the mescaline biosynthetic pathway in peyote (Lophophora williamsii). Plant Journal 116, 635-649 
• Ozber, N., Yu, L., Hagel, J.M., Facchini, P.J. (2023) Strong feedback inhibition of key enzymes in the morphine biosynthetic pathway from opium poppy detectable in engineered yeast. ACS Chemical Biology 18, 419-430
• Menéndez-Perdomo, I.M, Facchini, P.J. (2023) Elucidation of the (R)-enantiospecific benzylisoquinoline alkaloid biosynthetic pathways in sacred lotus (Nelumbo nucifera). Scientific Reports 13, 2955
• Ozber, N., Carr, S.C., Morris, J.S., Liang, S., Watkins, J.L., Caldo, K.M., Hagel, J.M., Ng, K.K.S., Facchini, P.J. (2022)Alkaloid binding to opium poppy major latex proteins triggers structural modification and functional aggregation. Nature Communications 13, 6768
• Ozber, N., Facchini, P.J. (2022) Phloem-specific localization of benzylisoquinoline alkaloid metabolism in opium poppy. Journal of Plant Physiology 271, 153641 
• Watkins, J.L., Facchini, P.J. (2022) Compartmentalization at the interface of primary and alkaloid metabolism. Current Opinion in Plant Biology 66, 102186
• Carr, S.C., Torres, M.A., Morris, J.S., Facchini, P.J., Ng, K.K.S. (2021) Structural studies of codeinone reductase reveal novel insights into aldo-keto reductase function in benzylisoquinoline alkaloid biosynthesis. Journal of Biological Chemistry 297, 101211
• Li, Q., Morris J.S., Facchini, P.J., Yeaman, S. (2021) Partial genome assembly of the medicinal plant Ephedra sinica. Biorxiv https://doi.org/10.1101/2021.06.02.446745
• Menéndez-Perdomo, I.M., Hagel, J.M., Facchini, P.J. (2021) LTQ-Orbitrap mass spectrometry in the analysis of benzylisoquinoline alkaloids in plants. Journal of Mass Spectrometry 56, e4683
• Morris, J.S., Caldo, K.M.P., Liang, S., Facchini, P.J. (2021) PR10/Betv1-like proteins as novel contributors to plant biochemical diversity. ChemBioChem 22, 264-287
• Ozber, N., Watkins, J., Facchini, P.J. (2020) Back to the plant: Overcoming roadblocks to the microbial production of pharmaceutically important plant natural products. Journal of Industrial Microbiology and Biotechnology 47, 815-828
• Chen, R., Chen X., Hagel, J.M., Facchini, P.J. (2020) Virus-induced gene silencing to investigate alkaloid biosynthesis in opium poppy. In: Virus-Inducd Gene Silencing in Plants: Methods and Protocols (Courdavault, V. and Besseau, S., eds). Methods in Molecular Biology 2172, 75-92
• Li, Q., Ramasamy, S., Singh, P., Hagel, J.M., Dunemann, S., Chen, X., Chen, R., Yu, L., Tucker, J.E., Facchini, P.J., Yeaman, S. (2020) Gene clustering and copy number variation in alkaloid metabolic pathways of opium poppy. Nature Communications 11, 1190
• Menéndez-Perdomo, I.M., Facchini, P.J. (2020) Isolation and characterization of two O-methyltransferases involved in benzylisoquinoline alkaloid biosynthesis in sacred lotus (Nelumbo nucifera). Journal of Biological Chemistry 295, 1598-1612
• Singh, A., Menéndez-Perdomo, I.M., Facchini, P.J. (2019) Benzylisoquinoline alkaloid biosynthesis in opium poppy - an update. Phytochemistry Reviews 18, 1457-1482
• Morris, J.S., Yu, L., Facchini, P.J. (2019) A single residue determines substrate preference in benzylisoquinoline N-methyltransferases. Phytochemistry 170, 112193
• Dastmalchi, M., Chang, L., Chen, R., Yu, L., Chen, X., Hagel, J.M., Facchini, P.J. (2019) Purine permease-type benzylisoquinoline alkaloid transporters in opium poppy. Plant Physiology doi:10.1104/pp.19.00565
• Singh, A., Menéndez-Perdomo, I.M., Facchini, P.J. (2019) Benzyisoquinoline alkaloid biosynthesis in opium poppy - an update. Phytochemistry Reviews doi:10.1007/s11101-019-09644-w
• Lang, D.E., Morris, J.E., Rowley, M., Torres, M.A., Maksimovich, V.A., Facchini, P.J., Ng, K.K.S. (2019) Structure-function studies of tetrahydroprotoberberine N-methyltransferase reveal the molecular basis of stereoselective substrate recognition. Journal of Biological Chemistry 294, 14482-14498
• Morris, J.S., Facchini, P.J. (2019) Molecular origins of functional diversity of benzylisoquinoline alkaloid methyltransferases. Frontiers in Plant Science doi:10.3389/fpls.2019.01058
• Dastmalchi, M., Chen, X., Hagel, J.M., Chang, L., Chen, R., Ramasamy, S., Yeaman, S., Facchini, P.J. (2019) Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy. Nature Chemical Biology 15, 384-390
• Menendez-Perdomo, I.M., Facchini, P.J. (2018) Benzylisoquinoline alkaloid biosynethsis in sacred lotus. Molecules 23, 2899
• Hagel, J.M., Chen, X., Facchini, P.J. (2018) Production of methylparaben in Escherichia coli. Journal of Inductrial Microbiology and Biotechnology 46, 91-99
• 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 293, 13364-13376
• 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

Active Patents

• Compositions And Methods For Making (R)-Reticuline And Precursors Thereof (CA2932448C, granted, licensed)
• Compositions And Methods For Making (S)-Norcoclaurine And (S)-Norlaudanosoline, And Synthesis Intermediates Thereof (CA2952638A1, granted, licensed)
• Polynucleotides and Polypeptides Useful for Making Alkaloid Compounds ((CA2952638A1, granted, licensed)
• Improved Methods For Making And Using Polynucleotide Sequences In The Synthesis Of Alkaloid Compound (WO2015164960A1, pending)
• Neopinone Isomerase And Methods Of Using (CA3121827A1, pending, licenced)
• Compositions And Methods For Making Benzylisoquinoline Alkaloids, Morphinan Alkaloids, Thebaine, And Derivatives Thereof (US20220205004A1, pending, licensed)
• Compositions And Methods For Making Noscapine And Synthesis Intermediates Thereof (CA2921468A1, abandoned, licensed)
• Purine Permeases and Methods of Using (WO2019113710A1, pending)
• C4-Carboxylic Acid Tryptamine Derivatives and Methods of Using (PCT/CA2022/051228, granted)
• C4-Carbonothioate Tryptamine Derivatives and Methods of Using (PCT/CA2022/051266, granted)
• C4-Tryptamine Derivatives and Methods of Using (PCT/CA2023/050352, pending)
• Salts of C4-Tryptamine Derivatives and Methods of Using (PCT/CA2023/050354, pending)
• Glycosylated Psilocybin Derivatives and Methods of Using (PCT/CA2021/051185, granted)
• Aminated Psilocybin Derivatives and Methods of Using (PCT/CA2022/050007, granted)
• Carboxylated Psilocybin Derivatives and Methods of Using (PCT/CA2021/051712, granted)
• Aldehyde and Ketone Derivatives of Psilocybin and Methods of Using (PCT/CA2021/051729, granted)
• Prenylated Psilocybin Derivatives and Methods of Using (PCT/CA2022/050091, granted)
• Multi-substituent Psilocybin Derivatives and Methods of Using (PCT/CA2022/050206, granted)
• Nitrilated Psilocybin Derivatives and Methods of Using (PCT/CA2021/051647, granted)
• Nitrated Psilocybin Derivatives and Methods of Using (PCT/CA2021/051214, pending)
• Halogenated Psilocybin Derivatives and Methods of Using (PCT/CA2021/051209, pending)
• Hydroxylated Psilocybin Derivatives and Methods of Using (PCT/CA2021/051210
• Tri-Halo-Alkoxy-Substituted Trypatamine Derivatives (PCT/CA2024/448483, pending)
• Glycosylated Mescaline Derivatives and Methods of Using (PCT/CA2022/051792, pending)
• Glycosylated Isopropylamine Mescaline Derivatives and Methods of Using (PCT/CA2022/051793, pending)
• Phosphorylated and Sulfonated Mescaline Derivatives and Methods of Using (PCT/CA2022/051412, pending)
• Isopropylamine Analogies of Phosphorylated and Sulfonated Mescaline Derivatives (WO2023108296A1, pending)
• Fused Heterocycle Mescaline Derivatives (PCT/CA2022/051846, pending)
• C1-Isoproylamine Fused Heterocyclic Mescaline Derivatives (PCT/CA2023/051041, pending)
• Substituted N-Propylamine Fused Heterocyclic Mescaline Derivatives (PCT/CA2023/051422, pending)
• Substituted Ethylamine Fused Heterocyclic Mescaline Derivatives (PCT/CA2023/051548, pending)

Entrepreneurship

• Co-founder and Chief Scientific Officer, Epimeron Inc., 2014-2019
• Co-founder and Chief Scientific Officer, Sertürner Inc., 2016-2019
• Co-Founder and Chief Operations Officer, Vindolon, Inc., (2016-2019)
• Co-Founder and Chief Scientific Officer, Willow Biosciences Inc. (TSX:WLLW), 2019-2020
• Co-founder and Chief Scientific Officer, MagicMed Industries Inc., 2020-2021
• Co-Founder and Chief Innovation Officer, Enveric Biosciences, Inc. (NASDAQ:ENVR), 2021-present