Reaction participants Show >> << Hide
- Name help_outline dihydroprecondylocarpine acetate Identifier CHEBI:142770 Charge 1 Formula C23H29N2O4 InChIKeyhelp_outline QXQMGTOURBIIKD-RUMUXARQSA-N SMILEShelp_outline C12=C(C=CC=C1)NC=3[C@]([C@@]4(C(C=[N+](CC4)CCC32)CC)[H])(C(=O)OC)COC(C)=O 2D coordinates Mol file for the small molecule Search links Involved in 5 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,365 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (+)-vincadifformine Identifier CHEBI:142830 Charge 1 Formula C21H27N2O2 InChIKeyhelp_outline GIGFIWJRTMBSRP-NJDAHSKKSA-O SMILEShelp_outline C=1(C[C@@]2([C@]3([NH+](CCC2)CC[C@@]43C5=C(NC41)C=CC=C5)[H])CC)C(=O)OC 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline acetate Identifier CHEBI:30089 (CAS: 71-50-1) help_outline Charge -1 Formula C2H3O2 InChIKeyhelp_outline QTBSBXVTEAMEQO-UHFFFAOYSA-M SMILEShelp_outline CC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 186 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,372 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:58588 | RHEA:58589 | RHEA:58590 | RHEA:58591 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
|
Publications
-
Completion of the canonical pathway for assembly of anticancer drugs vincristine/vinblastine in Catharanthus roseus.
Qu Y., Safonova O., De Luca V.
The important anticancer drugs, vinblastine, vincristine and analogs, are composed of the monoterpenoid indole alkaloids (MIAs), catharanthine and vindoline, found uniquely in the medicinal plant, Catharanthus roseus. While 26 genes involved in the assembly of these two MIAs are known, two key rea ... >> More
The important anticancer drugs, vinblastine, vincristine and analogs, are composed of the monoterpenoid indole alkaloids (MIAs), catharanthine and vindoline, found uniquely in the medicinal plant, Catharanthus roseus. While 26 genes involved in the assembly of these two MIAs are known, two key reactions have eluded characterization to complete the documentation of the vinblastine pathway in this plant species. The assembly of these dimeric MIAs requires O-acetylstemmadenine oxidase (ASO) and a dual function geissoschizine synthase (GS) that reduces cathenamine to form geissoschizine, and that also reduces the ASO product to form a common intermediate for subsequent conversion by four separate hydrolases to catharanthine, tabersonine or vincadifformine, respectively. The in planta role of ASO is supported by identifying a single amino acid-substituted ASO mutant with very low enzyme activity and by virus-induced gene silencing of ASO to produce plants that accumulate O-acetylstemmadenine rather than catharanthine and vindoline found in wild-type (WT) plants. The in planta role of GS is supported by showing that a low GS-expressing mutant accumulating lower levels of catharanthine and vindoline also displays significantly lower tabersonine-forming activity in coupled enzyme assays than in the WT background. Gene expression analyses demonstrate that both ASO and GS are highly enriched in the leaf epidermis where the pathways for catharanthine and tabersonine biosynthesis are expressed. The full elucidation of this canonical pathway enables synthetic biology approaches for manufacturing a broad range of MIAs, including these dimers used in cancer treatment. << Less
Plant J. 97:257-266(2019) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
-
The assembly of (+)-vincadifformine- and (-)-tabersonine-derived monoterpenoid indole alkaloids in Catharanthus roseus involves separate branch pathways.
Williams D., Qu Y., Simionescu R., De Luca V.
The biological activity of monoterpenoid indole alkaloids (MIAs) has led to their use in cancer treatment and other medical applications. Their biosynthesis has involved the formation of reactive intermediates by responsible enzymes to elaborate several different chemical scaffolds. Modification o ... >> More
The biological activity of monoterpenoid indole alkaloids (MIAs) has led to their use in cancer treatment and other medical applications. Their biosynthesis has involved the formation of reactive intermediates by responsible enzymes to elaborate several different chemical scaffolds. Modification of scaffolds through different substitution reactions has produced chemically diverse MIAs and related biological activities. The present study characterizes the three-step pathway involved in the formation of (+)-echitovenine, the major O-acetylated MIA of Catharanthus roseus roots, and differentiates it from a parallel pathway involved in the formation of hörhammericine. Separate hydrolases convert a common reactive MIA intermediate to aspidosperma skeletons of opposite specific rotations, that is (+)-vincadifformine and (-)-tabersonine, respectively. The formation of (+) minovincinine from (+) vincadifformine 19-hydroxylase (V19H) is catalyzed by a root-specific cytochrome P450 with high amino acid sequence similarity to the leaf-specific tabersonine-3-hydroxylase involved in vindoline biosynthesis. Similarly, O-acetylation of (+)-minovincinine to form (+) echitovenine involves minovincinine-O-acetytransferase. The substrate specificity of V19H and MAT for their respective (+)-enantiomers defines the separate enantiomer-specific pathway involved in (+)-echitovenine biosynthesis and differentiates it from a parallel (-)-enantiomer-specific pathway involved in the formation of hörhammericine from (-)-tabersonine. << Less
Plant J. 99:626-636(2019) [PubMed] [EuropePMC]
This publication is cited by 9 other entries.