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Information on EC 1.14.14.175 - ferruginol synthase and Organism(s) Salvia miltiorrhiza and UniProt Accession S4UX02

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IUBMB Comments
A cytochrome P-450 (heme thiolate) enzyme found in some members of the Lamiaceae (mint family). The enzyme from Rosmarinus officinalis (rosemary) is involved in biosynthesis of carnosic acid, while the enzyme from the Chinese medicinal herb Salvia miltiorrhiza is involved in the biosynthesis of the tanshinones, abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components found in the plant.
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This record set is specific for:
Salvia miltiorrhiza
UNIPROT: S4UX02
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Word Map
The taxonomic range for the selected organisms is: Salvia miltiorrhiza
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyp76ah1, cyp76ah24, cyp76ah4, ferruginol synthase, miltiradiene oxidase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CYP76AH1
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
abieta-8,11,13-triene,[reduced NADPH-hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)
A cytochrome P-450 (heme thiolate) enzyme found in some members of the Lamiaceae (mint family). The enzyme from Rosmarinus officinalis (rosemary) is involved in biosynthesis of carnosic acid, while the enzyme from the Chinese medicinal herb Salvia miltiorrhiza is involved in the biosynthesis of the tanshinones, abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components found in the plant.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
abieta-8,11,13-triene + [reduced NADPH-hemoprotein reductase] + O2
abieta-8,11,13-trien-12-ol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
?
abieta-8,11,13-triene + [reduced NADPH-hemoprotein reductase] + O2
ferruginol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
additional information
?
-
CYP76AH1, catalyzes a four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo
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-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
abieta-8,11,13-triene + [reduced NADPH-hemoprotein reductase] + O2
abieta-8,11,13-trien-12-ol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
?
abieta-8,11,13-triene + [reduced NADPH-hemoprotein reductase] + O2
ferruginol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
?
additional information
?
-
CYP76AH1, catalyzes a four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo
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-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P-450
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-
cytochrome P450
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-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.013
abieta-8,11,13-triene
pH 7.5, 28°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.4
abieta-8,11,13-triene
pH 7.5, 28°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
the enzyme catalyzes the first committed step in the biosynthesis of tanshinones, pathay overview
physiological function
CYP76AH1 catalyzes the conversion of the carbon skeleton miltiradiene into the intermediate ferruginol, which is involved in the biosynthesis of tanshinones, the chief bioactive ingredients of Salvia miltiorrhiza
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CYPH1_SALMI
495
1
55520
Swiss-Prot
Secretory Pathway (Reliability: 5)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D301E/N303S/V479F
mutation leads to a second oxidation of product to give 11-hydroxyferruginol, i.e. reaction of EC 1.14.14.60
additional information
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Saccharomyces cerevisiae
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
establishment of miltiradiene production in Saccharomyces cerevisiae. Incorporation of CYP76AH1 and phyto-CYP reductase genes lead to heterologous production of ferruginol at 10.5 mg/l
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ma, Y.; Ma, X.H.; Meng, F.Y.; Zhan, Z.L.; Guo, J.; Huang, L.Q.
RNA interference targeting CYP76AH1 in hairy roots of Salvia miltiorrhiza reveals its key role in the biosynthetic pathway of tanshinones
Biochem. Biophys. Res. Commun.
477
155-160
2016
Salvia miltiorrhiza (S4UX02), Salvia miltiorrhiza
Manually annotated by BRENDA team
Scheler, U.; Brandt, W.; Porzel, A.; Rothe, K.; Manzano, D.; Bozic, D.; Papaefthimiou, D.; Balcke, G.; Henning, A.; Lohse, S.; Marillonnet, S.; Kanellis, A.; Ferrer, A.; Tissier, A.
Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast
Nat. Commun.
7
12942
2016
Salvia fruticosa, Salvia miltiorrhiza (S4UX02), Salvia miltiorrhiza, Salvia rosmarinus
Manually annotated by BRENDA team
Guo, J.; Zhou, Y.J.; Hillwig, M.L.; Shen, Y.; Yang, L.; Wang, Y.; Zhang, X.; Liu, W.; Peters, R.J.; Chen, X.; Zhao, Z.K.; Huang, L.
CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts
Proc. Natl. Acad. Sci. USA
110
12108-12113
2013
Salvia miltiorrhiza (S4UX02)
Manually annotated by BRENDA team