Research is aimed at understanding the genetics, biochemistry, cellular biology, and molecular physiology of plant specialized metabolism with a focus on benzylisoquinoline alkaloids (e.g. morphine) in opium poppy, cannabinoids (e.g. cannabidiol) in cannabis, and phenylalkylamines (e.g. pseudoephedrine) in ephedra. Major foci include biosynthetic and ancilliary gene isolation, pathway elucidation, and mechanisms of metabolic regulation, although interests encompass a wide range of competencies from plant genome analysis to protein structural biology. The availability of an extensive toolbox of genes and an increasingly accurate set of assembly instructions has created unprecedented metabolic engineering opportunities in plants and microorganisms. Yeast strains producing a variety of natural and synthetic high-value plant metabolites are engineered and used for both basic research and commercial applications.

Recent Publications

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Ozber, N., Yu, L., Hagel, J.M., Facchini, P.J. (2023) Strong feedback inhibition of key enzymes inthe morphine biosynthetic pathway from opium poppy detectable in engineered yeast. ACS Chemical Biology (in press)
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 protein aggregation. Nature Communications https://doi.org/10.1038/s41467-022-34313-6
Ozber, N., Facchini, P.J. (2022) Phloem-specific localization of benzylisoquinoline alkaloid metabolism in opium poppy. Journal of Plant Physiology https://doi.org/10.1016/j.jplph.2022.153641
Watkins, J.L., Facchini, P.J. (2022) Compartmentalization at the interface of primary and alkaloid metabolism. Current Opinion in Plant Biology https://doi.org/10.1016/j.pbi2022.102186
Carr, S., 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 https://doi.org/10.1016/j.jbc.2021.101211
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) Benzylisoquinoline alkaloid analysis using high-resolution Orbitrap LC-MSⁿ. Journal of Mass Spectrometry 56, e4683
Morris, J.S., Caldo, K.M., Liang, S., Facchini, P.J. (2021) PR10/Bet v 1-like proteins as novel contributors to plant biochemical diversity. ChemBioChem 22, 264-287
Ozber, N., Watkins, J., Facchini, P.J. (2020) Back to the pant: 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) Benzyisoquinoline 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 181, 916-933
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.