Enzymes
UniProtKB help_outline | 1 proteins |
Enzyme class help_outline |
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Reaction participants Show >> << Hide
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
reduced [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11964
Reactive part
help_outline
- Name help_outline FMNH2 Identifier CHEBI:57618 (Beilstein: 6258176) help_outline Charge -2 Formula C17H21N4O9P InChIKeyhelp_outline YTNIXZGTHTVJBW-SCRDCRAPSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])([O-])=O)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 771 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline taxusin Identifier CHEBI:63664 (CAS: 19605-80-2) help_outline Charge 0 Formula C28H40O8 InChIKeyhelp_outline SKJSIVQEPKBFTJ-HUWILPJBSA-N SMILEShelp_outline [H][C@@]1(C[C@@]2([H])C[C@]3([H])C(=C)[C@H](CC[C@@]3(C)[C@@H](OC(C)=O)[C@H](OC(C)=O)C(=C1C)C2(C)C)OC(C)=O)OC(C)=O 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 7β-hydroxytaxusin Identifier CHEBI:63665 Charge 0 Formula C28H40O9 InChIKeyhelp_outline CNURLWAZNDLNMK-CNZAUHOSSA-N SMILEShelp_outline [H][C@@]1(C[C@@]2([H])C[C@]3([H])C(=C)[C@H](C[C@H](O)[C@@]3(C)[C@@H](OC(C)=O)[C@H](OC(C)=O)C(=C1C)C2(C)C)OC(C)=O)OC(C)=O 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 H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
oxidized [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11965
Reactive part
help_outline
- Name help_outline FMN Identifier CHEBI:58210 Charge -3 Formula C17H18N4O9P InChIKeyhelp_outline ANKZYBDXHMZBDK-SCRDCRAPSA-K SMILEShelp_outline C12=NC([N-]C(C1=NC=3C(N2C[C@@H]([C@@H]([C@@H](COP(=O)([O-])[O-])O)O)O)=CC(=C(C3)C)C)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 781 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:31975 | RHEA:31976 | RHEA:31977 | RHEA:31978 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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MetaCyc help_outline |
Publications
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Molecular cloning and characterization of a cytochrome P450 taxoid 2alpha-hydroxylase involved in Taxol biosynthesis.
Chau M., Croteau R.
The Taxol biosynthetic pathway, arising from the primary isoprenoid precursors isopentenyl diphosphate and dimethylallyl diphosphate in yew (Taxus), consists of approximately twenty steps, at least nine of which are thought to be cytochrome P450-mediated oxygenations. Several oxygenases involved i ... >> More
The Taxol biosynthetic pathway, arising from the primary isoprenoid precursors isopentenyl diphosphate and dimethylallyl diphosphate in yew (Taxus), consists of approximately twenty steps, at least nine of which are thought to be cytochrome P450-mediated oxygenations. Several oxygenases involved in the early hydroxylation steps of the pathway have been identified and the corresponding genes have been cloned; however, defining the enzymes and their genes responsible for oxygenations in the central portion of the pathway is more difficult because neither the exact sequence of reactions nor the relevant intermediates are known. A surrogate substrate, (+)-taxusin (taxa-4(20),11(12)-dien-5alpha,9alpha,10beta,13alpha-tetraol tetraacetate), that was previously employed in the isolation of a taxoid 7beta-hydroxylase, was used here to functionally screen a family of cytochrome P450 oxygenases originating from a Taxus cell EST library. This in vivo screen in yeast led to the identification of a 1488bp cDNA clone (encoding a 495 residue protein) that was capable of producing 2alpha-hydroxytaxusin from taxusin with a K(m) value of 10.5 +/-2.7 microM and k(cat) of about 0.05 s(-1) for the surrogate substrate. This structurally typical cytochrome P450 resembles most closely the previously isolated taxoid 7beta-hydroxylase, which also uses taxusin as a substrate, and both 2alpha- and 7beta-hydroxylases are capable of the reciprocal conversion of their respective pentaol tetraacetate products to the common hexaol tetraacetate. This C2-hydroxylase would appear to mediate the mid-pathway functionalization of the C2-position of the taxane core that ultimately bears a benzoyl group as an important Taxol pharmacophore. Overexpression of this cytochrome P450 taxoid 2alpha-hydroxylase in Taxus cells may improve Taxol yields and could prove useful in the production of other 2alpha-hydroxy taxoids as starting materials for subsequent acylation at this position. << Less
Arch. Biochem. Biophys. 427:48-57(2004) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450 taxoid 7 beta-hydroxylase.
Chau M., Jennewein S., Walker K., Croteau R.
Biosynthesis of the anticancer drug Taxol in yew species involves eight cytochrome P450-mediated oxygenations and four coenzyme A-dependent acylations of the diterpenoid core. A family of cytochrome P450 genes, obtained from a yew cell cDNA library, were functionally expressed and screened with ta ... >> More
Biosynthesis of the anticancer drug Taxol in yew species involves eight cytochrome P450-mediated oxygenations and four coenzyme A-dependent acylations of the diterpenoid core. A family of cytochrome P450 genes, obtained from a yew cell cDNA library, were functionally expressed and screened with taxusin (taxa-4(20),11(12)-dien-5 alpha,9 alpha,10 beta,13 alpha-tetraol tetraacetate) as a surrogate substrate. One clone converted this substrate to an oxygenated derivative that was identified as 7 beta-hydroxytaxusin. The structure and properties of this 7 beta-hydroxylase are similar to those of other taxoid hydroxylases. Kinetic and binding assays indicated selectivity of the 7 beta-hydroxylase for polyoxygenated and acylated taxoid substrates, an observation consistent with the operation of this enzyme in the central portion of the Taxol biosynthetic pathway. Although the 7 beta-hydroxyl of Taxol is not essential for antimitotic activity, this functional group provides a convenient means for preparing taxoid derivatives. << Less
Chem. Biol. 11:663-672(2004) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.