Alkaloid biosynthesis: metabolism and trafficking.

Alkaloids represent a highly diverse group of compounds that are related only by the occurrence of a nitrogen atom in a heterocyclic ring. Plants are estimated to produce approximately 12,000 different alkaloids, which can be organized into groups according to their carbon skeletal structures. Alkaloid biosynthesis in plants involves many catalytic steps, catalyzed by enzymes that belong to a wide range of protein families. The characterization of novel alkaloid biosynthetic enzymes in terms of structural biochemistry, molecular and cell biology, and biotechnological applications has been the focus of research over the past several years. The application of genomics to the alkaloid field has accelerated the discovery of cDNAs encoding previously elusive biosynthetic enzymes. Other technologies, such as large-scale gene expression analyses and metabolic engineering approaches with transgenic plants, have provided new insights into the regulatory architecture of alkaloid metabolism.

[1]  Kiyotaka Okada,et al.  A genetic regulatory network in the development of trichomes and root hairs. , 2008, Annual review of plant biology.

[2]  R. Jetter,et al.  Sealing plant surfaces: cuticular wax formation by epidermal cells. , 2008, Annual review of plant biology.

[3]  W. Roos,et al.  Regulatory interaction of the Galpha protein with phospholipase A2 in the plasma membrane of Eschscholzia californica. , 2007, The Plant journal : for cell and molecular biology.

[4]  L. Gavilano,et al.  Isolation and characterization of the cytochrome P450 gene CYP82E5v2 that mediates nicotine to nornicotine conversion in the green leaves of tobacco. , 2007, Plant & cell physiology.

[5]  S. Panjikar,et al.  Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries. , 2007, Chemistry & biology.

[6]  A. J. Fist,et al.  Metabolic engineering of morphinan alkaloids by over-expression and RNAi suppression of salutaridinol 7-O-acetyltransferase in opium poppy. , 2007, Plant biotechnology journal.

[7]  A. Becker,et al.  Highly efficient virus-induced gene silencing (VIGS) in California poppy (Eschscholzia californica): an evaluation of VIGS as a strategy to obtain functional data from non-model plants. , 2007, Annals of botany.

[8]  J. Koepke,et al.  Molecular Architecture of Strictosidine Glucosidase: The Gateway to the Biosynthesis of the Monoterpenoid Indole Alkaloid Family[W] , 2007, The Plant Cell Online.

[9]  A. Winkler,et al.  6-S-Cysteinylation of Bi-covalently Attached FAD in Berberine Bridge Enzyme Tunes the Redox Potential for Optimal Activity* , 2007, Journal of Biological Chemistry.

[10]  P. Facchini,et al.  Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis: an enzymatic Pictet-Spengler reaction. , 2007, Biochemistry.

[11]  M. Rodríguez-Concepcíon,et al.  Spatial distribution and hormonal regulation of gene products from methyl erythritol phosphate and monoterpene-secoiridoid pathways in Catharanthus roseus , 2007, Plant Molecular Biology.

[12]  R. Nawrot,et al.  Proteomic analysis of Chelidonium majus milky sap using two-dimensional gel electrophoresis and tandem mass spectrometry. , 2007, Phytochemistry.

[13]  P. Facchini,et al.  Molecular Cloning and Characterization of Tetrahydroprotoberberine cis-N-Methyltransferase, an Enzyme Involved in Alkaloid Biosynthesis in Opium Poppy* , 2007, Journal of Biological Chemistry.

[14]  G. Pasquali,et al.  Identification of a Bipartite Jasmonate-Responsive Promoter Element in the Catharanthus roseus ORCA3 Transcription Factor Gene That Interacts Specifically with AT-Hook DNA-Binding Proteins1[W] , 2007, Plant Physiology.

[15]  Fumihiko Sato,et al.  Knockdown of berberine bridge enzyme by RNAi accumulates (S)-reticuline and activates a silent pathway in cultured California poppy cells , 2007, Transgenic Research.

[16]  A. McCarthy,et al.  The Structure of Two N-Methyltransferases from the Caffeine Biosynthetic Pathway1[W][OA] , 2007, Plant Physiology.

[17]  Christoph W. Sensen,et al.  Gene transcript and metabolite profiling of elicitor-induced opium poppy cell cultures reveals the coordinate regulation of primary and secondary metabolism , 2007, Planta.

[18]  J. Ziegler,et al.  Molecular Modeling and Site-Directed Mutagenesis Reveal the Benzylisoquinoline Binding Site of the Short-Chain Dehydrogenase/Reductase Salutaridine Reductase1[W][OA] , 2007, Plant Physiology.

[19]  F. Sato,et al.  Functional Analysis of Norcoclaurine Synthase in Coptis japonica* , 2007, Journal of Biological Chemistry.

[20]  T. Kutchan,et al.  Metabolic engineering with a morphine biosynthetic P450 in opium poppy surpasses breeding. , 2007, Metabolic engineering.

[21]  F. Sato,et al.  Molecular cloning and characterization of methylenedioxy bridge‐forming enzymes involved in stylopine biosynthesis in Eschscholzia californica , 2007, The FEBS journal.

[22]  J. Jelesko,et al.  Cloning and characterization of a Nicotiana tabacum methylputrescine oxidase transcript. , 2007, Phytochemistry.

[23]  K. Tamura,et al.  Overexpression of Coptis japonica norcoclaurine 6-O-methyltransferase overcomes the rate-limiting step in Benzylisoquinoline alkaloid biosynthesis in cultured Eschscholzia californica. , 2007, Plant & cell physiology.

[24]  M. Teuber,et al.  Putrescine N-methyltransferases—a structure–function analysis , 2007, Plant Molecular Biology.

[25]  M. T. Nielsen,et al.  Biochemical and molecular characterizations of nicotine demethylase in tobacco , 2006 .

[26]  H. Sano,et al.  Transgenic tobacco plants producing caffeine: a potential new strategy for insect pest control , 2006, Transgenic Research.

[27]  Carla Coltharp,et al.  Redesign of a central enzyme in alkaloid biosynthesis. , 2006, Chemistry & biology.

[28]  C. Ammer,et al.  Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis. , 2006, The Plant journal : for cell and molecular biology.

[29]  S. Tanksley,et al.  EST database for early flower development in California poppy (Eschscholzia californica Cham., Papaveraceae) tags over 6000 genes from a basal eudicot , 2006, Plant Molecular Biology.

[30]  C. Sensen,et al.  Expressed sequence tags from Madagascar periwinkle (Catharanthus roseus) , 2006, FEBS letters.

[31]  P. Facchini,et al.  The role of phloem sieve elements and laticifers in the biosynthesis and accumulation of alkaloids in opium poppy. , 2006, The Plant journal : for cell and molecular biology.

[32]  A. Glieder,et al.  Biochemical Evidence That Berberine Bridge Enzyme Belongs to a Novel Family of Flavoproteins Containing a Bi-covalently Attached FAD Cofactor* , 2006, Journal of Biological Chemistry.

[33]  B. Hause,et al.  Immunolocalisation of two tropinone reductases in potato (Solanum tuberosum L.) root, stolon, and tuber sprouts , 2006, Planta.

[34]  Á. Ravelo,et al.  Tailoring Tropane Alkaloid Accumulation in Transgenic Hairy Roots of Atropa baetica by Over-expressing the Gene Encoding Hyoscyamine 6β-hydroxylase , 2006, Biotechnology Letters.

[35]  W. Roos,et al.  The Gα Protein Controls a pH-Dependent Signal Path to the Induction of Phytoalexin Biosynthesis in Eschscholzia californica , 2006, The Plant Cell Online.

[36]  P. Covello,et al.  Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement. , 2006, Chemistry & biology.

[37]  V. Courdavault,et al.  Epidermis is a pivotal site of at least four secondary metabolic pathways in Catharanthus roseus aerial organs , 2006, Planta.

[38]  Matej Oresic,et al.  Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Koepke,et al.  The Structure of Rauvolfia serpentina Strictosidine Synthase Is a Novel Six-Bladed β-Propeller Fold in Plant Proteins[W] , 2006, The Plant Cell Online.

[40]  K. San,et al.  Expression of the Arabidopsis feedback-insensitive anthranilate synthase holoenzyme and tryptophan decarboxylase genes in Catharanthus roseus hairy roots. , 2006, Journal of biotechnology.

[41]  S. Panjikar,et al.  Heterologous expression, purification, crystallization and preliminary X-ray analysis of raucaffricine glucosidase, a plant enzyme specifically involved in Rauvolfia alkaloid biosynthesis. , 2006, Acta crystallographica. Section F, Structural biology and crystallization communications.

[42]  W. Roos,et al.  Sanguinarine reductase, a key enzyme of benzophenanthridine detoxification. , 2006, Plant, cell & environment.

[43]  Steven Henikoff,et al.  TILLING: practical single-nucleotide mutation discovery. , 2006, The Plant journal : for cell and molecular biology.

[44]  S. Tanksley,et al.  Coffee and tomato share common gene repertoires as revealed by deep sequencing of seed and cherry transcripts , 2005, Theoretical and Applied Genetics.

[45]  V. De Luca,et al.  Localization of tabersonine 16-hydroxylase and 16-OH tabersonine-16-O-methyltransferase to leaf epidermal cells defines them as a major site of precursor biosynthesis in the vindoline pathway in Catharanthus roseus. , 2005, The Plant journal : for cell and molecular biology.

[46]  R. Dewey,et al.  Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[47]  L. Hileman,et al.  Virus-induced gene silencing is an effective tool for assaying gene function in the basal eudicot species Papaver somniferum (opium poppy). , 2005, The Plant journal : for cell and molecular biology.

[48]  Xueyan Ma,et al.  Functional expression of an ajmaline pathway-specific esterase from Rauvolfia in a novel plant-virus expression system , 2005, Planta.

[49]  C. Ammer,et al.  Comparative macroarray analysis of morphine containing Papaver somniferum and eight morphine free Papaver species identifies an O-methyltransferase involved in benzylisoquinoline biosynthesis , 2005, Planta.

[50]  G. Fritzsch,et al.  Crystallization and preliminary X-ray analysis of native and selenomethionyl vinorine synthase from Rauvolfia serpentina. , 2005, Acta crystallographica. Section D, Biological crystallography.

[51]  Benjamin P. MacLeod,et al.  Evidence for the monophyletic evolution of benzylisoquinoline alkaloid biosynthesis in angiosperms. , 2005, Phytochemistry.

[52]  P. Facchini,et al.  Sanguinarine Biosynthesis Is Associated with the Endoplasmic Reticulum in Cultured Opium Poppy Cells after Elicitor Treatment1 , 2005, Plant Physiology.

[53]  Sang-Un Park,et al.  Cell Type–Specific Localization of Transcripts Encoding Nine Consecutive Enzymes Involved in Protoberberine Alkaloid Biosynthesis , 2005, The Plant Cell Online.

[54]  P. Zhu,et al.  Molecular Cloning, Expression and Characterization of Hyoscyamine 6β-Hydroxylase from Hairy Roots of Anisodus tanguticus , 2005, Planta medica.

[55]  H. Sano,et al.  Caffeine Production in Tobacco Plants by Simultaneous Expression of Three Coffee N-methyltrasferases and Its Potential as a Pest Repellant , 2005, Plant Molecular Biology.

[56]  J. van der Greef,et al.  Proteome analysis of the medicinal plant Catharanthus roseus , 2005, Planta.

[57]  L. van der Fits,et al.  Zinc Finger Proteins Act as Transcriptional Repressors of Alkaloid Biosynthesis Genes in Catharanthus roseus* , 2004, Journal of Biological Chemistry.

[58]  T. Kutchan,et al.  Transformation of opium poppy (Papaver somniferumL.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots , 2004, Transgenic Research.

[59]  R. Hänsch,et al.  Polyphyletic Origin of Pyrrolizidine Alkaloids within the Asteraceae. Evidence from Differential Tissue Expression of Homospermidine Synthase1 , 2004, Plant Physiology.

[60]  A. J. Fist,et al.  RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy , 2004, Nature Biotechnology.

[61]  R. Dixon,et al.  Colocalization of l-Phenylalanine Ammonia-Lyase and Cinnamate 4-Hydroxylase for Metabolic Channeling in Phenylpropanoid Biosynthesis , 2004, The Plant Cell Online.

[62]  N. Nurhayati,et al.  Repeated Evolution of the Pyrrolizidine Alkaloid–Mediated Defense System in Separate Angiosperm Lineages w⃞ , 2004, The Plant Cell Online.

[63]  K. San,et al.  Metabolic engineering of the indole pathway in Catharanthus roseus hairy roots and increased accumulation of tryptamine and serpentine. , 2004, Metabolic engineering.

[64]  A. J. Fist,et al.  Analgesia: Morphine-pathway block in top1 poppies , 2004, Nature.

[65]  J. Ziegler,et al.  The roles of latex and the vascular bundle in morphine biosynthesis in the opium poppy, Papaver somniferum. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[66]  P. Facchini,et al.  Molecular cloning and characterization of norcoclaurine synthase, an enzyme catalyzing the first committed step in benzylisoquinoline alkaloid biosynthesis. , 2004, The Plant journal : for cell and molecular biology.

[67]  P. Giavalisco,et al.  Proteomics of curcurbit phloem exudate reveals a network of defence proteins. , 2004, Phytochemistry.

[68]  Xueyan Ma,et al.  Acetyltransfer in natural product biosynthesis--functional cloning and molecular analysis of vinorine synthase. , 2004, Bioorganic & medicinal chemistry.

[69]  D. Robertson VIGS vectors for gene silencing: many targets, many tools. , 2004, Annual review of plant biology.

[70]  B. Winkel,et al.  Metabolic channeling in plants. , 2004, Annual review of plant biology.

[71]  K. Oksman-Caldentey,et al.  Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[72]  H. Sano,et al.  Application of RNAi to confirm theobromine as the major intermediate for caffeine biosynthesis in coffee plants with potential for construction of decaffeinated varieties , 2004, Plant Molecular Biology.

[73]  M. Zenk,et al.  1,2-Dehydroreticuline synthase, the branch point enzyme opening the morphinan biosynthetic pathway. , 2004, Phytochemistry.

[74]  V. Burlat,et al.  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. , 2004, The Plant journal : for cell and molecular biology.

[75]  B. Dräger Chemistry and biology of calystegines. , 2004, Natural product reports.

[76]  T. Hartmann Plant-derived secondary metabolites as defensive chemicals in herbivorous insects: a case study in chemical ecology , 2004, Planta.

[77]  F. Lottspeich,et al.  (R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum - cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy. , 2003, The Plant journal : for cell and molecular biology.

[78]  R. Viola,et al.  Synthesis of L-ascorbic acid in the phloem , 2003, BMC Plant Biology.

[79]  P. Facchini,et al.  A Tale of Three Cell Types: Alkaloid Biosynthesis Is Localized to Sieve Elements in Opium Poppy Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.015396. , 2003, The Plant Cell Online.

[80]  F. Sato,et al.  Molecular Cloning and Characterization of CYP719, a Methylenedioxy Bridge-forming Enzyme That Belongs to a Novel P450 Family, from cultured Coptis japonica Cells* , 2003, Journal of Biological Chemistry.

[81]  Sang-Un Park,et al.  Developmental and inducible accumulation of gene transcripts involved in alkaloid biosynthesis in opium poppy. , 2003, Phytochemistry.

[82]  T. Fujimura,et al.  The first committed step reaction of caffeine biosynthesis: 7‐methylxanthosine synthase is closely homologous to caffeine synthases in coffee (Coffea arabica L.)1 , 2003, FEBS letters.

[83]  D. Inzé,et al.  A functional genomics approach toward the understanding of secondary metabolism in plant cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[84]  H. Sano,et al.  RNA interference: Producing decaffeinated coffee plants , 2003, Nature.

[85]  C. Kutter,et al.  Enzymes of jasmonate biosynthesis occur in tomato sieve elements. , 2003, Plant & cell physiology.

[86]  H. Sano,et al.  Molecular Cloning and Functional Characterization of Three Distinct N-Methyltransferases Involved in the Caffeine Biosynthetic Pathway in Coffee Plants1 , 2003, Plant Physiology.

[87]  Y. Yamazaki,et al.  Camptothecin biosynthetic genes in hairy roots of Ophiorrhiza pumila: cloning, characterization and differential expression in tissues and by stress compounds. , 2003, Plant & cell physiology.

[88]  G. Pertea,et al.  Comparative Analyses of Potato Expressed Sequence Tag Libraries1 , 2003, Plant Physiology.

[89]  O. Miersch,et al.  Selective desensitization of jasmonate- and pH-dependent signaling in the induction of benzophenanthridine biosynthesis in cells of Eschscholzia californica. , 2003, Phytochemistry.

[90]  T. Fujimura,et al.  Isolation of a new dual‐functional caffeine synthase gene encoding an enzyme for the conversion of 7‐methylxanthine to caffeine from coffee (Coffea arabica L.)1 , 2003, FEBS letters.

[91]  Kum-boo Choi,et al.  Molecular cloning of columbamine O-methyltransferase from cultured Coptis japonica cells. , 2002, European journal of biochemistry.

[92]  Yasuyuki Yamada,et al.  Expression patterns of two tobacco isoflavone reductase-like genes and their possible roles in secondary metabolism in tobacco , 2002, Plant Molecular Biology.

[93]  M. Blázquez,et al.  A Polyamine Metabolon Involving Aminopropyl Transferase Complexes in Arabidopsis Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.004077. , 2002, The Plant Cell Online.

[94]  Shujuan Gao,et al.  A Newly-Detected Reductase from Rauvolfia Closes a Gap in the Biosynthesis of the Antiarrhythmic Alkaloid Ajmaline , 2002, Planta medica.

[95]  P. Facchini,et al.  Purification and Characterization of Norcoclaurine Synthase , 2002, The Journal of Biological Chemistry.

[96]  T. Hartmann,et al.  Cell-Specific Expression of Homospermidine Synthase, the Entry Enzyme of the Pyrrolizidine Alkaloid Pathway in Senecio vernalis, in Comparison with Its Ancestor, Deoxyhypusine Synthase1 , 2002, Plant Physiology.

[97]  Shujuan Gao,et al.  Vomilenine reductase--a novel enzyme catalyzing a crucial step in the biosynthesis of the therapeutically applied antiarrhythmic alkaloid ajmaline. , 2002, Bioorganic & medicinal chemistry.

[98]  H. Decker,et al.  Potential active-site residues in polyneuridine aldehyde esterase, a central enzyme of indole alkaloid biosynthesis, by modelling and site-directed mutagenesis. , 2002, European Journal of Biochemistry.

[99]  Xueyan Ma,et al.  Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids. , 2002, European journal of biochemistry.

[100]  K. Nakajima,et al.  Molecular cloning, expression and characterization of tropinone reductase II, an enzyme of the SDR family in Solanum tuberosum (L.) , 2002, Plant Molecular Biology.

[101]  V. Loyola-Vargas,et al.  Overexpression in Catharanthus roseus hairy roots of a truncated hamster 3-hydroxy-3-methylglutaryl-CoA reductase gene , 2002, Applied biochemistry and biotechnology.

[102]  Sang-Un Park,et al.  Antisense RNA-Mediated Suppression of Benzophenanthridine Alkaloid Biosynthesis in Transgenic Cell Cultures of California Poppy1 , 2002, Plant Physiology.

[103]  Kum-boo Choi,et al.  Molecular Cloning and Characterization of CoclaurineN-Methyltransferase from Cultured Cells of Coptis japonica * , 2002, The Journal of Biological Chemistry.

[104]  J. Memelink,et al.  Geraniol 10‐hydroxylase1, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis , 2001, FEBS letters.

[105]  P. Facchini,et al.  Berberine bridge enzyme, a key branch-point enzyme in benzylisoquinoline alkaloid biosynthesis, contains a vacuolar sorting determinant , 2001, Planta.

[106]  T. Kutchan,et al.  Molecular Characterization of the Salutaridinol 7-O-Acetyltransferase Involved in Morphine Biosynthesis in Opium Poppy Papaver somniferum * , 2001, The Journal of Biological Chemistry.

[107]  H. Yamamoto,et al.  Secologanin synthase which catalyzes the oxidative cleavage of loganin into secologanin is a cytochrome P450. , 2001, Phytochemistry.

[108]  P. Facchini ALKALOID BIOSYNTHESIS IN PLANTS: Biochemistry, Cell Biology, Molecular Regulation, and Metabolic Engineering Applications. , 2001, Annual review of plant physiology and plant molecular biology.

[109]  N. Koizumi,et al.  7-Methylxanthine Methyltransferase of Coffee Plants , 2001, The Journal of Biological Chemistry.

[110]  P. Gantet,et al.  Catharanthus roseus G-box binding factors 1 and 2 act as repressors of strictosidine synthase gene expression in cell cultures , 2001, Plant Molecular Biology.

[111]  C. Nessler,et al.  Expression and activity of cell-wall-degrading enzymes in the latex of opium poppy, Papaver somniferum L. , 2001, Plant Molecular Biology.

[112]  M. Clastre,et al.  Cloning and expression of cDNAs encoding two enzymes of the MEP pathway in Catharanthus roseus. , 2000, Biochimica et biophysica acta.

[113]  S. Irmler,et al.  Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase. , 2000, The Plant journal : for cell and molecular biology.

[114]  F. Lottspeich,et al.  Characterization of proteins in latex of the opium poppy (Papaver somniferum) using two‐dimensional gel electrophoresis and microsequencing , 2000, Electrophoresis.

[115]  K. Nakajima,et al.  Ethylene suppresses jasmonate-induced gene expression in nicotine biosynthesis. , 2000, Plant & cell physiology.

[116]  R. Dixon,et al.  Genetic Manipulation of Isoflavone 7-O-Methyltransferase Enhances Biosynthesis of 4′-O-Methylated Isoflavonoid Phytoalexins and Disease Resistance in Alfalfa , 2000, Plant Cell.

[117]  A. Crozier,et al.  Plant biotechnology: Caffeine synthase gene from tea leaves , 2000, Nature.

[118]  T. Kutchan,et al.  Molecular cloning and functional bacterial expression of a plant glucosidase specifically involved in alkaloid biosynthesis. , 2000, Phytochemistry.

[119]  Yasuyuki Yamada,et al.  Molecular Characterization of theS-Adenosyl-l-methionine:3′-Hydroxy-N-methylcoclaurine 4′-O-Methyltransferase Involved in Isoquinoline Alkaloid Biosynthesis in Coptis japonica * , 2000, The Journal of Biological Chemistry.

[120]  L. van der Fits,et al.  ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and secondary metabolism. , 2000, Science.

[121]  S. Haebel,et al.  The gene encoding polyneuridine aldehyde esterase of monoterpenoid indole alkaloid biosynthesis in plants is an ortholog of the alpha/betahydrolase super family. , 2000, European journal of biochemistry.

[122]  T. Kutchan,et al.  Distribution of morphinan and benzo[c]phenanthridine alkaloid gene transcript accumulation in Papaver somninferum. , 2000, Phytochemistry.

[123]  J. Memelink,et al.  Molecular Cloning and Analysis of Strictosidine β-d-Glucosidase, an Enzyme in Terpenoid Indole Alkaloid Biosynthesis in Catharanthus roseus * , 2000, The Journal of Biological Chemistry.

[124]  T. Hartmann,et al.  Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[125]  B. Winkel-Shirley,et al.  Interactions among enzymes of the Arabidopsis flavonoid biosynthetic pathway. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[126]  G. Schröder,et al.  Light‐induced cytochrome P450‐dependent enzyme in indole alkaloid biosynthesis: tabersonine 16‐hydroxylase , 1999, FEBS letters.

[127]  J. Memelink,et al.  A novel jasmonate‐ and elicitor‐responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate‐ and elicitor‐inducible AP2‐domain transcription factor, ORCA2 , 1999, The EMBO journal.

[128]  T. Kutchan,et al.  Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum. , 1999, The Plant journal : for cell and molecular biology.

[129]  Yasuyuki Yamada,et al.  An Atropa belladonna hyoscyamine 6β-hydroxylase gene is differentially expressed in the root pericycle and anthers , 1999, Plant Molecular Biology.

[130]  F. Vázquez-Flota,et al.  Multicellular Compartmentation of Catharanthus roseus Alkaloid Biosynthesis Predicts Intercellular Translocation of a Pathway Intermediate , 1999, Plant Cell.

[131]  T. Kutchan,et al.  Molecular cloning and functional expression of O-methyltransferases common to isoquinoline alkaloid and phenylpropanoid biosynthesis. , 1999, The Plant journal : for cell and molecular biology.

[132]  R. Verpoorte,et al.  The iridoid glucoside secologanin is derived from the novel triose phosphate/pyruvate pathway in a Catharanthus roseus cell culture , 1998, FEBS letters.

[133]  B. Dierich,et al.  Chemical diversity and variation of pyrrolizidine alkaloids of the senecionine type: biological need or coincidence? , 1998, Planta.

[134]  G. Pasquali,et al.  Effects of over-expression of strictosidine synthase and tryptophan decarboxylase on alkaloid production by cell cultures of Catharanthus roseus , 1998, Planta.

[135]  A. Alarco,et al.  The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer. , 1998, The Plant journal : for cell and molecular biology.

[136]  M. Sottomayor,et al.  Purification and characterization of α‐3′,4′‐anhydrovinblastine synthase (peroxidase‐like) from Catharanthus roseus (L.) G. Don , 1998, FEBS letters.

[137]  T. Nakatsu,et al.  Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[138]  W. J. Lucas,et al.  An RNA-Based Information Superhighway in Plants , 1998, Science.

[139]  T. Kutchan,et al.  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. , 1998, The Plant journal : for cell and molecular biology.

[140]  M. López-Meyer,et al.  Tryptophan decarboxylase is encoded by two autonomously regulated genes in Camptotheca acuminata which are differentially expressed during development and stress. , 1997, The Plant journal : for cell and molecular biology.

[141]  F. Vázquez-Flota,et al.  Molecular cloning and characterization of desacetoxyvindoline-4-hydroxylase, a 2-oxoglutarate dependent-dioxygenase involved in the biosynthesis of vindoline in Catharanthus roseus (L.) G. Don , 1997, Plant Molecular Biology.

[142]  P. Facchini,et al.  Molecular Characterization of Berberine Bridge Enzyme Genes from Opium Poppy , 1996, Plant physiology.

[143]  Hideyuki Suzuki,et al.  Subcellular localization of acyltransferases for quinolizidine alkaloid biosynthesis in Lupinus , 1996 .

[144]  M. Zenk,et al.  Acetyl Coenzyme A:Salutaridinol-7-O-Acetyltransferase from Papaver somniferum Plant Cell Cultures: , 1995, The Journal of Biological Chemistry.

[145]  T. Schmidt,et al.  Sesquiterpene lactones and inositol esters from Arnica angustifolia. , 1995, Planta medica.

[146]  P. Facchini,et al.  Phloem-Specific Expression of Tyrosine/Dopa Decarboxylase Genes and the Biosynthesis of Isoquinoline Alkaloids in Opium Poppy. , 1995, The Plant cell.

[147]  M. Zenk,et al.  Purification and properties of codeinone reductase (NADPH) from Papaver somniferum cell cultures and differentiated plants. , 1995, European journal of biochemistry.

[148]  B. St-Pierre,et al.  A Cytochrome P-450 Monooxygenase Catalyzes the First Step in the Conversion of Tabersonine to Vindoline in Catharanthus roseus , 1995, Plant physiology.

[149]  J. Stöckigt,et al.  Enzymatic Formation of the Sarpagan-Bridge: A Key Step in the Biosynthesis of Sarpagine- and Ajmaline-Type Alkaloids , 1995, Planta medica.

[150]  T. Kutchan,et al.  Molecular cloning and heterologous expression of a cDNA encoding berbamunine synthase, a C--O phenol-coupling cytochrome P450 from the higher plant Berberis stolonifera. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[151]  J. Stöckigt,et al.  Enzymatic Biosynthesis of Vomilenine, a Key Intermediate of the Ajmaline Pathway, Catalyzed by a Novel Cytochrome P 450-Dependent Enzyme from Plant Cell Cultures of Rauwolfia serpentina , 1995 .

[152]  P. Facchini,et al.  Differential and tissue-specific expression of a gene family for tyrosine/dopa decarboxylase in opium poppy. , 1994, The Journal of biological chemistry.

[153]  Y. Yamada,et al.  Gene expression in tobacco low-nicotine mutants. , 1994, The Plant cell.

[154]  K. Nakajima,et al.  cDNA Encoding Tropinone Reductase-II from Hyoscyamus niger , 1993, Plant physiology.

[155]  Yasuyuki Yamada,et al.  Two tropinone reductases with different stereospecificities are short-chain dehydrogenases evolved from a common ancestor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[156]  M. Zenk,et al.  Purification and characterization of salutaridine: NADPH 7-oxidoreductase from Papaver somniferum , 1993 .

[157]  R. Verpoorte,et al.  Subcellular localization of tryptophan decarboxylase, strictosidine synthase and strictosidine glucosidase in suspension cultured cells of Catharanthus roseus and Tabernaemontana divaricata , 1993, Plant Cell Reports.

[158]  V. Luca,et al.  Partial purification of an N-methyltransferase involved in vindoline biosynthesis in Catharanthus roseus , 1993 .

[159]  M. Zenk,et al.  Formation of salutaridine from (R)-reticuline by a membrane-bound cytochrome P-450 enzyme from Papaver somniferum , 1992 .

[160]  Y. Yamada,et al.  Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[161]  M. Pšenák,et al.  Purification and characterization of dihydrobenzophenanthridine oxidase from elicited Sanguinaria canadensis cell cultures. , 1992, Archives of biochemistry and biophysics.

[162]  M. Zenk,et al.  Purification and properties of 1,2-dehydroreticuline reductase from Papaver somniferum seedlings , 1992 .

[163]  T. Kutchan,et al.  Molecular cloning, expression, and induction of berberine bridge enzyme, an enzyme essential to the formation of benzophenanthridine alkaloids in the response of plants to pathogenic attack. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[164]  T. McKnight,et al.  Expression of enzymatically active and correctly targeted strictosidine synthase in transgenic tobacco plants , 1991, Planta.

[165]  Y. Yamada,et al.  Molecular cloning of hyoscyamine 6 beta-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, from cultured roots of Hyoscyamus niger. , 1991, The Journal of biological chemistry.

[166]  Y. Yamada,et al.  Hyoscyamine 6 beta-hydroxylase, an enzyme involved in tropane alkaloid biosynthesis, is localized at the pericycle of the root. , 1991, The Journal of biological chemistry.

[167]  T. McKnight,et al.  Nucleotide sequence of a cDNA encoding the vacuolar protein strictosidine synthase from Catharanthus roseus. , 1990, Nucleic acids research.

[168]  T. Kutchan Expression of enzymatically active cloned strictosidine synthase from the higher plant Rauvolfia serpentina in Escherichia coli , 1989, FEBS letters.

[169]  C. Marineau,et al.  Molecular cloning and analysis of cDNA encoding a plant tryptophan decarboxylase: comparison with animal dopa decarboxylases. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[170]  A. Cutler,et al.  Subcellular Localization of Enzymes Involved in Indole Alkaloid Biosynthesis in Catharanthus roseus. , 1987, Plant physiology.

[171]  M. Zenk,et al.  Intracellular compartmentation of two enzymes of berberine biosynthesis in plant cell cultures , 1986, Planta.

[172]  J. Stöckigt,et al.  Late enzymes of vindoline biosynthesis , 1985, Plant Cell Reports.

[173]  M. Zenk,et al.  Purification and characterization of the berberine bridge enzyme from berberis beaniana cell cultures , 1985 .

[174]  T. Hartmann,et al.  Localization of the Enzymes of Quinolizidine Alkaloid Biosynthesis in Leaf Chloroplasts of Lupinus polyphyllus. , 1982, Plant physiology.

[175]  P. Facchini,et al.  Developmental regulation of benzylisoquinoline alkaloid biosynthesis in opium poppy plants and tissue cultures , 2008, In Vitro Cellular & Developmental Biology - Plant.

[176]  A. J. Fist,et al.  Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum. , 2007, Plant biotechnology journal.

[177]  F. Sato,et al.  Identification of a WRKY protein as a transcriptional regulator of benzylisoquinoline alkaloid biosynthesis in Coptis japonica. , 2007, Plant & cell physiology.

[178]  M. Teuber,et al.  Putrescine N-methyltransferase in Solanum tuberosum L., a calystegine-forming plant , 2005, Planta.

[179]  Sang-Un Park,et al.  Modulation of berberine bridge enzyme levels in transgenic root cultures of California poppy alters the accumulation of benzophenanthridine alkaloids , 2004, Plant Molecular Biology.

[180]  B. St-Pierre,et al.  Molecular and biochemical analysis of a Madagascar periwinkle root-specific minovincinine-19-hydroxy-O-acetyltransferase. , 2001, Plant physiology.

[181]  K. Nakajima,et al.  Structures and expression patterns of two tropinone reductase genes from Hyoscyamus niger. , 1999, Bioscience, biotechnology, and biochemistry.

[182]  K. Nakajima,et al.  Two tropinone reductases, that catalyze opposite stereospecific reductions in tropane alkaloid biosynthesis, are localized in plant root with different cell-specific patterns. , 1999, Plant & cell physiology.

[183]  Y. Yamada,et al.  Expression of Atropa belladonna putrescine N-methyltransferase gene in root pericycle. , 1999, Plant & cell physiology.

[184]  Yasuyuki Yamada,et al.  Molecular cloning and characterization of S-adenosyl-L-methionine:scoulerine-9-O-methyltransferase from cultured cells of Coptis japonica. , 1995, Plant & cell physiology.

[185]  M. Zenk,et al.  Two methylenedioxy bridge forming cytochrome P-450 dependent enzymes are involved in (S)-stylopine biosynthesis , 1991 .

[186]  M. Zenk,et al.  Elicitor induction and characterization of microsomal protopine-6-hydroxylase, the central enzyme in benzophenanthridine alkaloid biosynthesis , 1990 .

[187]  M. Zenk,et al.  Enzymatic formation of protopines by a microsomal cytochrome P-450 system of Corydalis vaginans , 1987 .