Non-statistical C-13 Fractionation Distinguishes Co-incident and Divergent Steps in the Biosynthesis of the Alkaloids Nicotine and Tropine
| Autor: | Richard J. Robins, Katarzyna M. Romek, Virginie Silvestre, Piotr Paneth, Gérald S. Remaud |
|---|---|
| Přispěvatelé: | Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0106 biological sciences
Reaction mechanism Nicotine Stereochemistry 01 natural sciences Biochemistry Isotopomers chemistry.chemical_compound Biosynthesis Kinetic isotope effect Tobacco medicine [CHIM]Chemical Sciences Carbon Radioisotopes Molecular Biology Hyoscyamine Tropine Isotope 010405 organic chemistry Cell Biology Carbon-13 NMR 0104 chemical sciences Metabolism chemistry 010606 plant biology & botany medicine.drug Tropanes |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291 (32), pp.16620-16629. ⟨10.1074/jbc.M116.734087⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M116.734087⟩ |
| Popis: | During the biosynthesis of natural products, isotopic fractionation occurs due to the selectivity of enzymes for the heavier or lighter isotopomers. As only some of the positions in the molecule are implicated in a given reaction mechanism, position-specific fractionation occurs, leading to a non-statistical distribution of isotopes. This can be accessed by isotope ratio monitoring (13)C NMR spectrometry. The solanaceous alkaloids S-(-)-nicotine and hyoscyamine (atropine) are related in having a common intermediate, but downstream enzymatic steps diverge, providing a relevant test case to: (a) elucidate the isotopic affiliation between carbon atoms in the alkaloids and those in the precursors; (b) obtain information about the kinetic isotope effects of as yet undescribed enzymes, thus to make predictions as to their possible mechanism(s). We show that the position-specific (13)C/(12)C ratios in the different moieties of these compounds can satisfactorily be related to their known precursors and to the known kinetic isotope effects of enzymes involved in their biosynthesis, or to similar reaction mechanisms. Thus, the pathway to the common intermediate, N-methyl-Δ(1)-pyrrolinium, is seen to introduce similar isotope distribution patterns in the two alkaloids independent of plant species, whereas the remaining atoms of each target compound, which are of different origins, reflect their specific metabolic ancestry. We further demonstrate that the measured (13)C distribution pattern can be used to deduce aspects of the reaction mechanism of enzymes still to be identified. |
| Databáze: | OpenAIRE |
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