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Plant cytochrome P450s directing monoterpene indole alkaloid (MIA) and benzylisoquinoline alkaloid (BIA) biosynthesis

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Abstract

The large family of cytochrome P450 enzymes are heme containing proteins generally associated with the cytoplasmic face of the endoplasmic reticulum in Eukaryotic cells. They play essential roles in detoxification mechanisms of cellular processes and are key components in biosynthesis and evolution of specialized metabolites having various biological activities in the plant kingdom. The assembly of complex monoterpenoid indole alkaloids and benzylisoquinoline alkaloids involves numerous cytochrome P450 enzymes that participate in their chemical diversification and that act as central scaffolds for recruitment of the biosynthetic enzymes required for their production. The present review discusses the roles played by different CYP families (-71, -72, -75, -76, 80-, 82-, -86 and -719) in the diversification of MIA and BIA pathways that have been discovered and characterized. Recent studies using homology model guided site-directed mutagenesis coupled with determination of biochemical function are described that provide insights about how small modifications in protein structures allowed the evolution of new substrate specificity and the appearance of new monoterpenoid indole alkaloids and benzylisoquinoline alkaloids in Nature.

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References

  • Abedini D, Monfared SR, Abbasi A (2018) The effects of promoter variation on the N-methylcanadine 1-hydroxylase (CYP82Y1) gene on the noscapine production in opium poppy. Sci Rep 8:4973

    Article  PubMed  PubMed Central  Google Scholar 

  • Beaudoin GAW, Facchini PJ (2013) Isolation and characterization of a cDNA encoding (S)-cis-N-methylstylopine 14-hydroxylase from opium poppy, a key enzyme in sanguinarine biosynthesis. Biochem Biophys Res Commun 431:597–603

    Article  CAS  PubMed  Google Scholar 

  • Besseau S, Kellner F, Lanou A, Thamm V, Schneider B, Geu-Flores F, Höfer R, Guirimand G, Guihur A, Oudin A, Glevarec G, Foureau E, Papon N, Clastre M, Giglioli-Guivarc’h, O’Connor, S.E., Courdavault, V. (2013) A pair of tabersonine 16-hydroxylase initiates the synthesis of vindoline in an organ-dependent manner in Catharanthus roesus. Plant Physiol 163:1792–1803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolwell GP, Bozak K, Zimmerlin A (1994) Plant cytochrome P450. Phytochemistry 37(6):1491–1506

    Article  CAS  PubMed  Google Scholar 

  • Burlat V, Oudin A, Courtois M, Rideau M, St-Pierre B (2004) Co-expression of three MEP pathway genes and geraniol 10-hydroxylase in internal phloem parenchyma of Catharanthus roseus implicates multicellular translocation of intermediates during the biosynthesis of monoterpene indole alkaloids and isoprenoid-derived primary metabolites. Plant J 38:131–141

    Article  CAS  PubMed  Google Scholar 

  • Carqueijeiro I, Dugé de Bernonville T, Lanoue A, Dang TT, Teijaro CN, Paetz C, Courdavault V (2018a) A BAHD acyltransferase catalyzing 19-O-acetylation of tabersonine derivatives in roots of Catharanthus roseus enables combinatorial synthesis of monoterpene indole alkaloids. Plant J 94(3):469–484

    Article  CAS  PubMed  Google Scholar 

  • Chapple C (1998) Molecular genetics analysis of plant cytochrome P450-dependent monooxygenases. Ann Rev Plant Physiol Mol Biol 49:311–343

    Article  CAS  Google Scholar 

  • Chávez MLD, Rolf M, Gesell A, Kutchan TM (2011) Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana. Arch Biochem Biophys 507:186–193

    Article  Google Scholar 

  • Cojocaru V, Winn PJ, Wade RC (2007) The ins and outs of cytochrome P450s. Biochem Biophys Acta 1770:390–401

    Article  CAS  PubMed  Google Scholar 

  • Colinas, M., Pollier, J., Vaneechoutte, D., Malat, D. G., Schweizer, F., De Clercq, R., Guedes, J. G., Martínez-Cortés, Hidalgo, F. J. M., Sottomayor, M., Vandepoele, K., Goossens, A (2020) A modular system regulates specialized metabolite pathway branch choice in the medicinal plant Catharanthus roseus. bioRxiv PREPRINT doi: https://doi.org/10.1101/2020.05.04.075671.

  • Collu G, Unver N, Peltenburg-Looman AMG, van der Heijden R, Verpoorte R, Memelink J (2001) Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett 508:215–220

    Article  CAS  PubMed  Google Scholar 

  • Dang T-T, Facchini PJ (2014a) Cloning and characterization of canadine synthase involved in noscapine biosynthesis in opium poppy. FEBS Lett 588:198–204

    Article  CAS  PubMed  Google Scholar 

  • Dang T-T, Facchini PJ (2014b) CYP82Y1 is N-methylcanadine 1-hydroxylase, a key noscapine biosynthetic enzyme in opium poppy. J Biol Chem 289:2013–2026

    Article  CAS  PubMed  Google Scholar 

  • Dang T-TT, Chen X, Facchini PJ (2015) Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nat Chem Biol 11:104–106

    Article  CAS  PubMed  Google Scholar 

  • Dang T-TT, Franke J, Tatsis E, O’Connor SE (2017) Dual catalytic activity of a cytochrome P450 controls bifurcation at a metabolic branch point of alkaloid biosynthesis in Rauvolfia serpentina. Angew Chem 129:9568–9572

    Article  Google Scholar 

  • Dang T-TT, Franke J, Carqueijeiro IST, Langley C, Courdavault V, O’Connor SE (2018) Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes. Nat Chem Biol 14:760–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dastmalchi M, Park MR, Morris JS, Facchini P (2018) Family portraits: the enzymes behind benzylisoquinoline alkaloid diversity. Phytochem Rev 17:249–277

    Article  CAS  Google Scholar 

  • De Luca V, Salim V, Thamm A, Masada SA, Yu F (2014) Making iridoids/secoiridoids and monoterpenoid indole alkaloids: progress on pathway elucidation. Curr Opin Plant Biol 19:35–42

    Article  PubMed  Google Scholar 

  • Denisov IG, Makris TM, Sligar SG, Schlichting I (2005) Structure and chemistry of cytochrome P450. Chem Rev 105:2253–2277

    Article  CAS  PubMed  Google Scholar 

  • Dugé de Bernonville T, Foureau E, Parage C, Lanoue A, Clastre M, Londono MA, Courdavault V (2015) Characterization of a second secologanin synthase isoform producing both secologanin and secoxyloganin allows enhanced de novo assembly of a Catharanthus roseus transcriptome. BMC Genomics 16(1):1–19

    Article  Google Scholar 

  • Dziggel C, Schäfer H, Wink M (2017) Tools of pathway reconstruction and production of economically relevant plant secondary metabolites in recombinant organisms. Biotechnol J 12:1600145

    Article  Google Scholar 

  • Edge A, Qu Y, Easson MLAE, Thamm AMK, Kim KH, De Luca V (2018) A tabersonine 3-reductase Catharanthus roseus mutant accumulates vindoline pathway intermediates. Planta 247(1):155–169

    Article  CAS  PubMed  Google Scholar 

  • Falkenhagen H, Stöckigt J (1995) Enzymatic biosynthesis of vomilenine, a key intermediate of the ajmaline pathway, catalysed by a novel cytochrome P-450-dependent enzyme from plant cell cultures of Rauvolfia serpentina. Z Naturforsch C: Biosci 50:45–53

    Article  CAS  Google Scholar 

  • Farrow SC, Kamileen MO, Meades J, Ameyaw B, Xiao Y, O’Connor S (2018) Cytochrome P450 and O-methyltransferase catalyze the final steps in the biosynthesis of the anti-addictive alkaloid ibogaine from Tabernanthe iboga. J Biol Chem 293(36):13821–13833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farrow SC, Hagel JM, Beaudoin GAW, Burns DC, Facchini PJ (2015) Stereochemical inversion of (S)-reticuline by a cytochrome p450 fusion in opium poppy. Nat Chem Biol 11:728–732

    Article  CAS  PubMed  Google Scholar 

  • Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret J-P, Beaudoin GAW, Facchini PJ, Martin VJJ (2013) Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae. Nat Commun 5:3283

    Article  Google Scholar 

  • Franke J, Kim J, Hamilton JP, Zha D, Pham GM, Weigert-Rininger K, Crisovan E, Newton L, Vaillancourt B, Tatsis E, Buell CR, O’Connor SE (2019) Gene discovery in Gelsemium highlights conserved gene clusters in monoterpene indole alkaloid biosynthesis. ChemBioChem 20:83–87

    Article  CAS  PubMed  Google Scholar 

  • Gandhi SG, Mahajan V, Bedi YS (2015) Changing trends in biotechnology of secondary metabolism in medicinal and aromatic plants. Planta 241:303–317

    Article  CAS  PubMed  Google Scholar 

  • Gesell A, Rolf M, Ziegler J, Chávez MLD, Huang F-C, Kutchan TM (2009) CYP719B1 is salutaridine synthase, the C-C phenol-coupling enzyme of morphine biosynthesis in opium poppy. J Biol Chem 284(36):24432–24442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giddings L-A, Liscombe DK, Hamilton JP, Childs KL, DellaPenna D, Buell CR, O’Connor SE (2011) A stereoselective hydroxylation step of alkaloid biosynthesis by a unique cytochrome P450 in Catharanthus roseus. J Biol Chem 286(19):16751–16757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotoh O (1992) Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences. J Biol Chem 267:83–90

    Article  CAS  PubMed  Google Scholar 

  • Hagel JM, Facchini PJ (2013) Benzylisoquinoline alkaloid metabolism: A century of discovery and a brave new world. Plant Cell Physiol 54(5):647–672

    Article  CAS  PubMed  Google Scholar 

  • Hallahan DL, West JM, Wallsgrove RM, Smiley DWM, Dawson GW, Pickette JA, Hamilton JGC (1995) Purification and characterization of an acyclic monoterpene primary alcohol: NADP+ oxidoreductase from cat-mint (Nepeta racemose). Arch Biochem Biophys 318:105–112

    Article  CAS  PubMed  Google Scholar 

  • Hamberger B, Bak S (2013) Plant P450s as versatile drivers of evolution of species-specific chemical diversity. Phil Trans R Soc B 368:20120426

    Article  PubMed  PubMed Central  Google Scholar 

  • Höfer R, Dong L, André F, Ginglinger J-F, Lugan R, Gavira C, Grec S, Lang G, Memelink J, Van Der Krol S, Bouwmeester H, Werck-Reichhart D (2013) Geraniol hydroxylase and hydroxygeraniol oxidase activities of the CYP76 family of cytochrome P450 enzymes and potential for engineering the early steps of the (seco)iridoid pathway. Metabolic Engineerin, g 20:221–232

    Article  Google Scholar 

  • Hori K, Yamada Y, Purwanto R, Minakuchi Y, Toyoda A, Hirakawa H, Sato F (2018) Mining of the uncharacterized cytochrome P450 genes involved in alkaloid biosynthesis in California poppy using a draft genome sequence. Plant Cell Physiol 59(2):222–233

    Article  CAS  PubMed  Google Scholar 

  • Huang F-C, Kutchan TM (2000) Distribution of morphinan and benzo[c]phenanthridine alkaloid gene transcript accumulation in Papaver somniferum. Phytochemistry 53:555–564

    Article  CAS  PubMed  Google Scholar 

  • Ikeda H, Esaki N, Nakai S, Hashimoto K, Uesato S, Soda K, Fujita T (1991) Acyclic monoterpene primary alcohol:NADP+ oxidoreductase of Rauwolfia serpentina cells: The key enzyme in biosynthesis of monoterpene alcohols. The Journal of Biochemistry 109(2):341–347

    CAS  PubMed  Google Scholar 

  • Ikezawa N, Tanaka M, Nagayoshi M, Shinkyo R, Sakaki T, Inouye K, Sato F (2003) Molecular cloning and characterization of CYP719, a methylenedioxy bridge-forming enzyme that belongs to a novel P450 family, form cultured Coptis japonica cells. J Biol Chem 278(40):38557–38565

    Article  CAS  PubMed  Google Scholar 

  • Ikezawa N, Iwasa K, Sato F (2007) Molecular cloning and characterization of methylenedioxy bridge-forming enzymes involved in stylopine biosynthesis in Eschscholzia californica. FEBS J 271:1019–1035

    Article  Google Scholar 

  • Ikezawa N, Iwasa K, Sato F (2008) Molecular cloning and characterization of CYP80G2, a cytochrome P450 that catalyzes an intramolecular C-C phenol coupling of (S)-reticuline in magnoflorine biosynthesis, from cultured Coptis japonica cells. J Biol Chem 283(14):8810–8821

    Article  CAS  PubMed  Google Scholar 

  • Ikezawa N, Iwasa K, Sato F (2009) CYP719A subfamily of cytochrome P450 oxygenases and isoquinoline alkaloid biosynthesis in Eschscholzia californica. Plant Cell Rep 28:123–133

    Article  CAS  PubMed  Google Scholar 

  • Irmler S, Schröder G, St-Pierre B, Crouch NP, Hotze M, Schmidt J, Strack D, Matern U, Schröder J (2000) Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase. Plant J 24(6):797–804

    Article  CAS  PubMed  Google Scholar 

  • Iyer RN, Favela D, Zhang G, Olson DE (2020) The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. Nat Prod Rep. https://doi.org/10.1039/d0np00033g

    Article  Google Scholar 

  • Jørgensen K, Rasmussen AV, Morant M, Nielsen AH, Bjarnholt N, Zagrobelny M, Bak S, B., Møller, B. L. (2005) Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr Opin Plant Biol 8:280–291

    Article  PubMed  Google Scholar 

  • Jun X, Xin-ya W, Wang-zhen G (2015) The cytochrome P450 superfamily: Key players in plant development and defense. J Integr Agric 14(9):1673–1686

    Article  Google Scholar 

  • Kellner F, Geu-Flores F, Sherden NH, Brown S, Foureau E, Courdavault V, O’Connor SE (2015) Discovery of a P450-catalyzed step in vindoline biosynthesis: a link between the aspidosperma and eburnamine alkaloids. Chem Commun 51:7626–7628

    Article  CAS  Google Scholar 

  • Kilgore, M. B., Augustin, M. M., May, G. D., Crow, J. A., Kutchan, T. M. (2016) CYP96T1 of Narcissus sp. aff. Pseudonarcissus catalyzes the formation of the para-para’ C-C phenol couple in the Amaryllidaceae alkaloids. Frontiers in Plant Science, 7, 225.

  • Kraus PFX, Kutchan TM (1995) Molecular cloning and heterologous expression of a cDNA encoding berbamunine synthase, a C-O phenol-coupling cytochrome P450 from the higher plant Berberis stolonifera. Proc Natl Acad Sci USA 92:2071–2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang J, An T, Zhu JX, Chen S, Zhu JH, Peters RJ, Yu R, Zi J (2021) Mining of the Catharanthus roseus Genome Leads to Identification of a Biosynthetic Gene Cluster for Fungicidal Sesquiterpenes. J Nat Prod 84:2709–2716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michener JK, Nielsen J, Smolke CD (2012) Identification and treatment of heme depletion attributed to overexpression of a lineage of evolved P450 monooxygenases. Proc Natl Acad Sci USA 109:19504–19509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miettinen K, Dong L, Navrot N, Schneider T, Burlat V, Pollier J, Woittiez L, van der Krol S, Lugan R, Ilc T, Verpoorte R, Oksman-Caldentey K-M, Martinoia E, Bouwmeester H, Goossens A, Memelink J, Werck-Reichhart D (2014) The secoiridoid pathway from Catharanthus roseus. Nat Commun 5:3606

    Article  PubMed  Google Scholar 

  • Nelson DR (2006) Plant cytochrome P450s from moss to poplar. Phytochem Rev 5:193–204

    Article  CAS  Google Scholar 

  • Nelson D, Werck-Reichhart D (2011) A P450-centric view of plant evolution. Plant J 66:194–211

    Article  CAS  PubMed  Google Scholar 

  • Nelson DR, Ming R, Maqsudul A, Schuler MA (2008) Comparison of cytochrome P450 genes from six plant genomes. Tropical Plant Biology 1:216–235

    Article  CAS  Google Scholar 

  • Nett RS, Lau W, Sattely ES (2020) Discovery and engineering of colchicine alkaloid biosynthesis. Nature 584:148–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen TD, Dang TT (2021) Cytochrome P450 Enzymes as Key Drivers of Alkaloid Chemical Diversification in Plants. Front Plant Sci 12:682181

    Article  PubMed  PubMed Central  Google Scholar 

  • Norwood VM, Huigens RW (2019) Harnessing the chemistry of the indole heterocycle to drive discoveries in biology and medicine. ChemBioChem 20:2273–2297

    Article  CAS  PubMed  Google Scholar 

  • Pauli HH, Kutchan TM (1998) Molecular cloning and functional heterologous expression of two alleles encoding (S)-N-methylcoclaurine 3’-hydroxylase (CYP80B1), a new methyl jasmonate-inducible cytochrome P-450-dependent mono-oxygenase of benzylisoquinoline alkaloid biosynthesis. Plant J 13(6):793–801

    Article  CAS  PubMed  Google Scholar 

  • Porter TD, Coon MJ (1991) Cytochrome P-450: Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 256(21):13469–13472

    Article  Google Scholar 

  • Qu Y, Easson MLAE, Froese J, Simionescu R, Hudlicky T, De Luca V (2015) Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast. Proc Natl Acad Sci USA 112(19):6224–6229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qu Y, Easson MLAE, Simionescu R, Hajicek J, Thamm AMK, Salim V, De Luca V (2018) Solution of the multistep pathway for assembly of corynanthean, strychnos, iboga, and aspidosperma monoterpenoid indole alkaloids from 19 E-geissoschizine. Proc Natl Acad Sci USA 115(12):3180–3185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ralston L, Yu O (2006) Metabolons involving plant cytochrome P450s. Phytochem Rev 5:459–472

    Article  CAS  Google Scholar 

  • Rather GA, Sharma A, Misra P, Kumar A, Kaul V, Lattoo SK (2020) Molecular characterization and overexpression analyses of secologanin synthase to understand the regulation of camptothecin biosynthesis in Nothapodytes nimmoniana (Graham.) Mabb. Protoplasma 257:391–405

    Article  PubMed  Google Scholar 

  • Renault H, Bassard JE, Hamberger B, Werck-Reichhart D (2014) Cytochrome P450-mediated metabolic engineering: Current progress and future challenges. Curr Opin Plant Biol 19:27–34

    Article  CAS  PubMed  Google Scholar 

  • Rosales PF, Bordin GS, Gower AE, Moura S (2020) Indole alkaloids: 2012 until now, highlighting the new chemical structures and biological activities. Fitoterapia 143:104558

    Article  CAS  PubMed  Google Scholar 

  • Salim V, Yu F, Altarejos J, De Luca V (2013) Virus-induced gene silencing identifies Catharanthus roseus 7-deoxyloganic acid-7-hydroxylase, a step in iridoid and monoterpene indole alkaloid biosynthesis. Plant J 76:754–765

    Article  CAS  PubMed  Google Scholar 

  • Salim V, Wiens B, Masada-Atsumi S, Yu F, De Luca V (2014) 7-deoxyloganetic acid synthase catalyzes a key 3-step oxidation to form 7-deoxyloganetic acid in Catharanthus roseus iridoid biosynthesis. Phytochemistry 101:23–31

    Article  CAS  PubMed  Google Scholar 

  • Sawada Y, Ayabe S-I (2005) Multiple mutagenesis of P450 isoflavonoid synthase reveals a key active-site residue. Biochem Biophys Res Commun 330:907–913

    Article  CAS  PubMed  Google Scholar 

  • Schläger S, Dräger B (2016) Exploiting plant alkaloids. Curr Opin Biotechnol 37:155–164

    Article  PubMed  Google Scholar 

  • Schoch GA, Attias R, Le Ret M, Werck-Reichhart D (2003) Key substrate recognition residues in the active site of a plant cytochrome P450, CYP73A1. Eur J Biochem 270:3684–3695

    Article  CAS  PubMed  Google Scholar 

  • Schrittwieser JH, Resch V (2013) The role of biocatalysis in the asymmetric synthesis of alkaloids. RSC Adv 3:17602

    Article  CAS  PubMed  Google Scholar 

  • Schröder J (1999) Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylase. FEBS Lett 458(2):97–102

    Article  PubMed  Google Scholar 

  • Schröder G, Unterbusch E, Kaltenbach M, Schmidt J, Strack D, De Luca V, Schröder J (1999) Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylase. FEBS Lett 458(2):97–102

    Article  PubMed  Google Scholar 

  • Srere PA (2000) Macromolecular interactions: tracing the roots. Trends Biochem Sci 25:150–153

    Article  CAS  PubMed  Google Scholar 

  • Stadler R, Zenk MH (1993) The purification and characterization of a unique cytochrome P450 enzyme from Berberis stolonifera plant cell cultures. J Biol Chem 268(2):823–831

    Article  CAS  PubMed  Google Scholar 

  • St-Pierre B, De Luca V (1995) A cytochrome P-450 monooxygenase catalyzes the first step in the conversion of tabersonine to vindoline in Catharanthus roseus. Plant Physiol 109:131–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung P-H, Huang F-C, Do Y-Y, Huang P-L (2011) Functional expression of geraniol 10-hydroxylase reveals its dual function in the biosynthesis of terpenoid and phenylpropanoid. J Agric Food Chem 59:4637–4643

    Article  CAS  PubMed  Google Scholar 

  • Takemura T, Ikezawa N, Iwasa K, Sato F (2013) Molecular cloning and characterization of a cytochrome P450 in sanguinarine biosynthesis from Eschscholzia californica cells. Phytochemistry 91:100–108

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Yang S, An B, Wang S, Yin S, Lu Y, Xu Y, Hao D (2011) Molecular dynamics analysis reveals structural insights into mechanism of nicotine N-demethylation catalyzed by tobacco cytochrome P450 monooxygenase. PLoS ONE 6(8):e23342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams D, Qu Y, Simionescu R, De Luca V (2019) The assembly of (+)-vincadifformine- and (-)-tabersonine-derived monoterpenoid indole alkaloids in Catharanthus roseus involves separate branch pathways. Plant J 99(4):626–636

    Article  CAS  PubMed  Google Scholar 

  • Williams, D., Brzezinski, W., Gordon, H., De Luca, V. (2022) Site directed mutagenesis of Catharanthus roseus (+)-vincadifformine 19-hydroxylase (CYP71BY3) results in two distinct enzymatic functions. Phytochemistry (in press).

  • Yang Y, Li W, Pang J, Jiang L, Qu X, Pu X, Zhang G, Luo Y (2019) Bifunctional cytochrome P450 enzymes involved in camptothecin biosynthesis. ACS Chem Biol 14:1091–1096

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (VDL), Canada Research Chairs (VDL) and the Advanced Biomanufacturing Center (Brock University) (VDL). DW was the recipient of a Queen Elizabeth II Graduate Scholarship in Science & Technology. Additional data reported in the study can be found in the Supporting Information.

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    Danielle Williams & Vincenzo De Luca

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Correspondence to Vincenzo De Luca.

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Williams, D., De Luca, V. Plant cytochrome P450s directing monoterpene indole alkaloid (MIA) and benzylisoquinoline alkaloid (BIA) biosynthesis. Phytochem Rev 22, 309–338 (2023). https://doi.org/10.1007/s11101-022-09841-0

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