KEGG   ORTHOLOGY: K20513
Entry
K20513                      KO                                     
Symbol
CYP76AH1
Name
ferruginol synthase [EC:1.14.14.175]
Pathway
map00904  Diterpenoid biosynthesis
map01110  Biosynthesis of secondary metabolites
Reaction
R12652  abieta-8,11,13-triene,[reduced NADPH---hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K20513  CYP76AH1; ferruginol synthase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   00199 Cytochrome P450
    K20513  CYP76AH1; ferruginol synthase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.14  With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.14.175  ferruginol synthase
     K20513  CYP76AH1; ferruginol synthase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, plant type
  CYP76 family
   K20513  CYP76AH1; ferruginol synthase
Genes
EGT: 105959240 105975178
SSPL: 121747525 121753304 121756002 121759934 121761842 121764980 121766436 121766444 121766445 121778538 121780327 121781922 121783193 121788445 121790206 121800549 121808049
SMIL: 130991308 130991309 130991327 130998360 131000178 131000189 131015954 131020581 131020582
SHIS: 125186032 125192328 125192396 125192722 125193616 125194755 125197829 125199011 125200770 125202661 125202663 125202849 125205027 125211802 125212140 125212654 125212704 125216734 125217682 125218657 125218856 125219752 125219893
APAN: 127265187
AG: AGN04215(CYP76AH1) AJQ30186(FS) AJQ30187(FS1)
Reference
PMID:23812755
  Authors
Guo J, Zhou YJ, Hillwig ML, Shen Y, Yang L, Wang Y, Zhang X, Liu W, Peters RJ, Chen X, Zhao ZK, Huang L
  Title
CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts.
  Journal
Proc Natl Acad Sci U S A 110:12108-13 (2013)
DOI:10.1073/pnas.1218061110
  Sequence
[ag:AGN04215]
Reference
PMID:26020634
  Authors
Bozic D, Papaefthimiou D, Bruckner K, de Vos RC, Tsoleridis CA, Katsarou D, Papanikolaou A, Pateraki I, Chatzopoulou FM, Dimitriadou E, Kostas S, Manzano D, Scheler U, Ferrer A, Tissier A, Makris AM, Kampranis SC, Kanellis AK
  Title
Towards Elucidating Carnosic Acid Biosynthesis in Lamiaceae: Functional Characterization of the Three First Steps of the Pathway in Salvia fruticosa and  Rosmarinus officinalis.
  Journal
PLoS One 10:e0124106 (2015)
DOI:10.1371/journal.pone.0124106
  Sequence
[ag:AJQ30186 AJQ30187]
LinkDB

KEGG   ORTHOLOGY: K22636
Entry
K22636            Tight     KO                                     
Symbol
CYP76AH24
Name
ferruginol synthase / ferruginol monooxygenase [EC:1.14.14.175 1.14.14.60]
Pathway
map00904  Diterpenoid biosynthesis
map01110  Biosynthesis of secondary metabolites
Reaction
R11951  ferruginol,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (11-hydroxyferruginol forming)
R12652  abieta-8,11,13-triene,[reduced NADPH---hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K22636  CYP76AH24; ferruginol synthase / ferruginol monooxygenase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   00199 Cytochrome P450
    K22636  CYP76AH24; ferruginol synthase / ferruginol monooxygenase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.14  With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.14.60  ferruginol monooxygenase
     K22636  CYP76AH24; ferruginol synthase / ferruginol monooxygenase
    1.14.14.175  ferruginol synthase
     K22636  CYP76AH24; ferruginol synthase / ferruginol monooxygenase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, plant type
  CYP76 family
   K22636  CYP76AH24; ferruginol synthase / ferruginol monooxygenase
Genes
AG: ALM25796(CYP76AH24)
Reference
PMID:26976595
  Authors
Ignea C, Athanasakoglou A, Ioannou E, Georgantea P, Trikka FA, Loupassaki S, Roussis V, Makris AM, Kampranis SC
  Title
Carnosic acid biosynthesis elucidated by a synthetic biology platform.
  Journal
Proc Natl Acad Sci U S A 113:3681-6 (2016)
DOI:10.1073/pnas.1523787113
  Sequence
[ag:ALM25796]
LinkDB

KEGG   ENZYME: 1.14.14.175
Entry
EC 1.14.14.175              Enzyme                                 
Name
ferruginol synthase;
miltiradiene oxidase (incorrect);
CYP76AH1;
miltiradiene,NADPH:oxygen oxidoreductase (ferruginol forming) (incorrect)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
Sysname
abieta-8,11,13-triene,[reduced NADPH---hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)
Reaction(IUBMB)
abieta-8,11,13-triene + [reduced NADPH---hemoprotein reductase] + O2 = ferruginol + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R12652]
Reaction(KEGG)
R12652
Substrate
abieta-8,11,13-triene [CPD:C21425];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
O2 [CPD:C00007]
Product
ferruginol [CPD:C09092];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001]
Comment
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.
History
EC 1.14.14.175 created 2014 as EC 1.14.13.190, modified 2015, transferred 2020 to EC 1.14.14.175
Pathway
ec00904  Diterpenoid biosynthesis
ec01110  Biosynthesis of secondary metabolites
Orthology
K20513  ferruginol synthase
K22636  ferruginol synthase / ferruginol monooxygenase
Genes
EGT: 105959240 105975178
SSPL: 121747525 121753304 121756002 121759934 121761842 121764980 121766436 121766444 121766445 121778538 121780327 121781922 121783193 121788445 121790206 121800549 121808049
SMIL: 130991308 130991309 130991327 130998360 131000178 131000189 131015954 131020581 131020582
SHIS: 125186032 125192328 125192396 125192722 125193616 125194755 125197829 125199011 125200770 125202661 125202663 125202849 125205027 125211802 125212140 125212654 125212704 125216734 125217682 125218657 125218856 125219752 125219893
APAN: 127265187
Reference
1  [PMID:23812755]
  Authors
Guo J, Zhou YJ, Hillwig ML, Shen Y, Yang L, Wang Y, Zhang X, Liu W, Peters RJ, Chen X, Zhao ZK, Huang L
  Title
CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts.
  Journal
Proc Natl Acad Sci U S A 110:12108-13 (2013)
DOI:10.1073/pnas.1218061110
  Sequence
[ag:AGN04215]
Reference
2  [PMID:24108414]
  Authors
Zi J, Peters RJ
  Title
Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae.
  Journal
Org Biomol Chem 11:7650-2 (2013)
DOI:10.1039/c3ob41885e
Reference
3  [PMID:26020634]
  Authors
Bozic D, Papaefthimiou D, Bruckner K, de Vos RC, Tsoleridis CA, Katsarou D, Papanikolaou A, Pateraki I, Chatzopoulou FM, Dimitriadou E, Kostas S, Manzano D, Scheler U, Ferrer A, Tissier A, Makris AM, Kampranis SC, Kanellis AK
  Title
Towards Elucidating Carnosic Acid Biosynthesis in Lamiaceae: Functional Characterization of the Three First Steps of the Pathway in Salvia fruticosa and  Rosmarinus officinalis.
  Journal
PLoS One 10:e0124106 (2015)
DOI:10.1371/journal.pone.0124106
  Sequence
[ag:AJQ30186 AJQ30187]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.14.175
IUBMB Enzyme Nomenclature: 1.14.14.175
ExPASy - ENZYME nomenclature database: 1.14.14.175
BRENDA, the Enzyme Database: 1.14.14.175
LinkDB

KEGG   REACTION: R12652
Entry
R12652                      Reaction                               
Name
abieta-8,11,13-triene,[reduced NADPH---hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)
Definition
Abieta-8,11,13-triene + [Reduced NADPH---hemoprotein reductase] + Oxygen <=> Ferruginol + [Oxidized NADPH---hemoprotein reductase] + H2O
Equation
C21425 + C03024 + C00007 <=> C09092 + C03161 + C00001
Enzyme
1.14.14.175
Pathway
rn00904  Diterpenoid biosynthesis
rn01110  Biosynthesis of secondary metabolites
Brite
Enzymatic reactions [BR:br08201]
 1. Oxidoreductase reactions
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.14  With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.14.175
     R12652  Abieta-8,11,13-triene + [Reduced NADPH---hemoprotein reductase] + Oxygen <=> Ferruginol + [Oxidized NADPH---hemoprotein reductase] + H2O
Orthology
K20513  ferruginol synthase [EC:1.14.14.175]
K22636  ferruginol synthase / ferruginol monooxygenase [EC:1.14.14.175 1.14.14.60]
LinkDB

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