Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity

Nature Communications

Volumn 7, Issue , 2016, Pages

  Stavrinides, Anna ^a   Tatsis, Evangelos C ^a   Caputi, Lorenzo ^a   Foureau, Emilien ^b   Stevenson, Clare E M ^a   Lawson, David M ^a   Courdavault, Vincent ^b   O'Connor, Sarah E ^a  

^a JOHN INNES CENTRE   (United Kingdom)

^b UNIVERSITÉ DE TOURS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AGLYCONE; ALCOHOL DEHYDROGENASE; ALKALOID DERIVATIVE; HETEROYOHIMBINE ALKALOID; OXIDOREDUCTASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; STRICTOSIDINE; UNCLASSIFIED DRUG; PLANT PROTEIN; RAUWOLFIA ALKALOID; VINCA ALKALOID;

ALKALOID; BIOACTIVITY; CHEMICAL REACTION; ENZYME ACTIVITY; GENE EXPRESSION; HERB; METABOLISM; MOLECULAR ANALYSIS; SECONDARY METABOLITE;

ARTICLE; BIODIVERSITY; BIOSYNTHESIS; CATHARANTHUS ROSEUS; CELLULAR DISTRIBUTION; CHEMICAL STRUCTURE; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DIASTEREOISOMER; GENE SILENCING; HETERONUCLEAR MULTIPLE BOND CORRELATION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLIC ENGINEERING; NUCLEAR LOCALIZATION SIGNAL; PLANT METABOLISM; PROTEIN FAMILY; PROTON NUCLEAR MAGNETIC RESONANCE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STEREOCHEMISTRY; CATHARANTHUS; CELL NUCLEUS; CHEMISTRY; ENZYME ACTIVE SITE; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOLECULAR CLONING; MOLECULAR DOCKING; MOLECULAR MODEL; PROTEIN CONFORMATION; SITE DIRECTED MUTAGENESIS; STEREOISOMERISM;

CATHARANTHUS ROSEUS;

CATALYTIC DOMAIN; CATHARANTHUS; CELL NUCLEUS; CLONING, MOLECULAR; GENE EXPRESSION REGULATION, PLANT; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; MUTAGENESIS, SITE-DIRECTED; PLANT PROTEINS; PROTEIN CONFORMATION; SECOLOGANIN TRYPTAMINE ALKALOIDS; STEREOISOMERISM; VINCA ALKALOIDS;

EID: 84978758732     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms12116     Document Type: Article

References (67)

1. Shamma, M. & Richey, J. M. The stereochemistry of the heteroyohimbine alkaloids. J. Am. Chem. Soc. 85, 2507-2512 (1963).
2. Allain, H. & Bentue-Ferrer, D. Clinical efficacy of almitrine-raubasine. An overview. Eur. Neurol. 39, 39-44 (1998).
3. Benzi, G. Pharmacological features of an almitrine-raubasine combination. Activity at cerebral levels. Eur. Neurol. 39, 31-38 (1998).
4. Li, S. et al. Assessment of the therapeutic activity of a combination of almitrine and raubasine on functional rehabilitation following ischaemic stroke. Curr. Med. Res. Opin. 20, 409-415 (2004).
5. Roquebert, J. & Demichel, P. Inhibition of the a1-and a2-adrenoceptormediated pressor response in pithed rats by raubasine, tetrahydroalstonine and akuammigine. Eur. J. Pharmacol. 106, 203-205 (1984).
6. Ai, J., Dekermendjian, K., Nielsen, M. & Witt, M. R. The heteroyohimbine mayumbine binds with high affinity to rat brain benzodiazepine receptors in vitro. Nat. Prod. Lett. 11, 73-76 (1997).
7. Dassonneville, L. et al. Stimulation of topoisomerase II-mediated DNA cleavage by three DNA-intercalating plant alkaloids: cryptolepine, matadine, and serpentine. Biochemistry 38, 7719-7726 (1999).
8. Costa-Campos, L., Iwu, M. & Elisabetsky, E. Lack of pro-convulsant activity of the antipsychotic alkaloid alstonine. J. Ethnopharmacol. 93, 3017-3310 (2004).
9. Elisabetsky, E. & Costa-Campos, L. The alkaloid alstonine: A review of Its pharmacological properties. eCAM 3, 39-48 (2006).
10. Herrmann, A. P. et al. Effects of the putative antipsychotic alstonine on glutamate uptake in acute hippocampal slices. Neurochem. Int. 61, 1144-1150 (2012).
11. Linck, V. M. et al. Alstonine as an antipsychotic: effects on brain amines and metabolic changes. eCAM, 418597 (2011).
12. Linck, V. M. et al. 5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine. Prog. Neuropsychopharmacol. Biol. Psychiatry 36, 29-33 (2012).
13. Linck, V. M. et al. Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida). Phytomedicine 22, 52-55 (2015).
14. Saxton, J. E. The Chemistry of Heterocyclic Compounds, Indoles: the Monoterpenoid Indole Alkaloids (Wiley, 2009).
15. Amer, M. A. & Court, W. E. P. Alkaloids of Rauwolfia nitida root bark. Phytochemistry 20, 2569-2573 (1981).
16. Hochstein, F. A. Alkaloids of Rauwolfia sellowii. J. Am. Chem. Soc. 77, 5744-5745 (1955).
17. Melchio, J., Bouquet, A., Pais, M. & Goutarel, R. Alcaloides indoliques CVI (1) Identité de la mayumbine et de l'épi-19 ajmalicine. L'iso-3 rauniticine, un nouvel alcalo ïde extrait du Corynanthe mayumbensis (R. Good) N. Hallé. Tetrahedron Lett. 18, 315-316 (1977).
18. Phillipson, J. D. & Supavita, N. Alkaloids of uncaria elliptica. Phytochemistry 22, 1809-1813 (1983).
19. Ponglux, D., Supavita, T., Verpoorte, R. & Phillipson, D. P. Alkaloids of Uncaria attenuata from Thailand. Phytochemistry 19, 2013-2016 (1980).
20. Robinson, R. & Thomas, A. F. The alkaloids of picralima nitida, Stapf, Th. and H. Durand. Part I. The structure of alkuammigine. J. Chem. Soc. 3479-3482 (1954).
21. Stoeckigt, J., Husson, H. P., Kan-Fan, C. & Zenk, M. H. Cathenamine, a central intermediate in the cell free biosynthesis of ajmalicine and related indole alkaloids. J. Chem. Soc. Chem. Commun. 164-166 (1977).
22. O'Connor, S. E. & Maresh, J. J. Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat. Prod. Rep. 23, 532-547 (2006).
23. Gerasimenko, I., Sheludko, Y., Ma, X. & Stöckigt, J. Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids. Eur. J. Biochem. 269, 2204-2213 (2002).
24. Stavrinides, A. et al. Unlocking the diversity of alkaloids in Catharanthus roseus: nuclear localization suggests metabolic channeling in secondary metabolism. Chem. Biol. 22, 336-341 (2015).
25. Gongora-Castillo, E. et al. Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species. PloS ONE 7, e52506 (2012).
26. Kellner, F. et al. Genome-guided investigation of plant natural product biosynthesis. Plant J. 82, 680-692 (2015).
27. Bomati, E. K. & Noel, J. P. Structural and kinetic basis for substrate selectivity in Populus tremuloides sinapyl alcohol dehydrogenase. Plant Cell 17, 1698-1611 (2005).
28. Pan, H. et al. Structural studies of cinnamoyl-CoA reductase and cinnamylalcohol dehydrogenase, key enzymes of monolignol biosynthesis. Plant Cell 26, 3709-3727 (2014).
29. Youn, B. et al. Crystal structures and catalytic mechanism of the Arabidopsis cinnamyl alcohol dehydrogenases AtCAD5 and AtCAD4. Org. Biomol. Chem. 4, 687-1697 (2006).
30. Auld, D. S. & Bergman, T. Medium-and short-chain dehydrogenase/reductase gene and protein families: The role of zinc for alcohol dehydrogenase structure and function. Cell. Mol. Life Sci. 65, 3961-3970 (2008).
31. Eklund, H. & Ramaswamy, S. Medium-and short-chain dehydrogenase/reductase gene and protein families: Three-dimensional structures of MDR alcohol dehydrogenases. Cell. Mol. Life Sci. 65, 3907-3917 (2008).
32. Stoeckigt, J., Hemscheidt, T., Hoefle, G., Heinstein, P. & Formacek, V. Steric course of hydrogen transfer during enzymatic formation of 3a-heteroyohimbine alkaloids. Biochemistry 22, 3448-3452 (1983).
33. Knowles, J. R. & Jencks, W. P. The intrinsic pka-values of functional groups in enzymes: Improper deductions from the ph-dependence of steady-state parameter. Crit. Rev. Biochem. 4, 165-173 (1976).
34. Guirimand, G. et al. Strictosidine activation in Apocynaceae: towards a "nuclear time bomb"? BMC Plant Biol. 10, 182 (2010).
35. Liscombe, D. K. & O'Connor, S. E. A virus-induced gene silencing approach to understanding alkaloid metabolism in Catharanthus roseus. Phytochemistry 72, 1969-1977 (2011).
36. Brown, S., Clastre, M., Courdavault, V. & O'Connor, S. E. De novo production of the plant-derived alkaloid strictosidine in yeast. Proc. Natl Acad. Sci. USA 112, 3205-3210 (2015).
37. Konno, K., Hirayama, C., Yasui, H. & Nakamura, M. Enzymatic activation of oleuropein: A protein crosslinker used as a chemical defense in the privet tree. Proc. Natl Acad. Sci. USA 96, 9159-9164 (1999).
38. Pankoke, H., Buschmann, T. & Muller, C. Role of plant beta-glucosidases in the dual defense system of iridoid glycosides and their hydrolyzing enzymes in Plantago lanceolata and Plantago major. Phytochemistry 94, 99-107 (2013).
39. Frelin, O. et al. A directed-overflow and damage-control N-glycosidase in riboflavin biosynthesis. Biochem. J. 466, 137-145 (2015).
40. Qu, Y. et al. 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, 6224-6229 (2015).
41. Berrow, N. S. et al. A versatile ligation-independent cloning method suitable for high-throughput expression screening applications. Nucleic Acids Res. 35, e45 (2007).
42. Kabsch, W. EDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125-132 (2010).
43. Evans, P. R. & Murshudov, G. N. Scaling and assessment of data quality. Acta Crystallogr. D Biol. Crystallogr. 69, 1204-1214 (2013).
44. Winter, G. Xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186-190 (2010).
45. Winter, G. & McAuley, K. E. Automated data collection for macromolecular crystallography. Methods 55, 81-93 (2011).
46. Sheldrick, G. M. A short history of SHELX. Acta Crystallogr. Sect. A 64, 112-122 (2008).
47. Delageniere, S. et al. ISPyB: an information management system for synchrotron macromolecular crystallography. Bioinformatics 27, 3186-3192 (2011).
48. Fisher, S. J., Levik, K. E., Williams, M. A., Ashton, A. W. & McAuley, K. E. SynchWeb: a modern interface for ISPyB. J. Appl. Crystallogr. 48, 927-932 (2015).
49. Cowtan, K. The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr. Sect. D 62, 1002-1011 (2006).
50. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
51. Winn, M. D., Murshudov, G. N. & Papiz, M. Z. Macromolecular TLS refinement in REFMAC at moderate resolutions. Methods Enzymol. 374, 300-321 (2003).
52. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
53. Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N. & Sternberg, M. J. The Phyre2 web portal for protein modeling, prediction and analysis. Nat. Protoc. 10, 845-858 (2015).
54. Painter, J. & Merritt, E. A. TLSMD web server for the generation of multi-group TLS models. J. Appl. Crystallogr 39, 109-111 (2006).
55. Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21 (2010).
56. McNicholas, S., Potterton, E., Wilson, K. S. & Noble, M. E. Presenting your structures: the CCP4mg molecular-graphics software. Acta Crystallogr. D Biol. Crystallogr. 67, 386-394 (2011).
57. Sun, J., Baker, A. & Chen, P. Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 25, 2591-2602 (2011).
58. Guirimand, G. et al. Optimization of the transient transformation of Catharanthus roseus cells by particle bombardment and its application to the subcellular localization of hydroxymethylbutenyl 4-diphosphate synthase and geraniol 10-hydroxylase. Plant Cell Rep. 28, 1215-1234 (2009).
59. Guirimand, G. et al. Spatial organization of the vindoline biosynthetic pathway in Catharanthus roseus. J. Plant Physiol. 168, 549-557 (2011).
60. Waadt, R. et al. Multicolor bimolecular fluorescence complementation reveals simultaneous formation of alternative CBL/CIPK complexes in planta. Plant J. 56, 505-516 (2008).
61. Geu-Flores, F. et al. An alternative route to cyclic terpenes by reductive cyclization. Nature 492, 138-142 (2012).
62. Kearse, M. et al. Geneious Basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647-1649 (2012).
63. Larkin, M. A. et al. Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947-2948 (2007).
64. Gouy, M., Guindon, S. & Gascuel, O. Seaview version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol. Biol. Evol. 27, 221-224 (2010)
65. Gouet, P., Robert, X. & Courcelle, E. ESPript/ENDscript: extracting and rendering sequence and 3D information from atomic structures of proteins. Nucleic Acids Res. 31, 3320-3323 (2003).
66. Saitou, N. & Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406-425 (1987).
67. Morris, G. M. et al. Autodock4 and autodocktools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785-2791 (2009).