KEGG   ORTHOLOGY: K14370Help
Entry
K14370                      KO                                     

Name
eryK, CYP113A
Definition
erythromycin 12 hydroxylase [EC:1.14.13.154]
Pathway
ko00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ko01052  Type I polyketide structures
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00774  Erythromycin biosynthesis, propanoyl-CoA + methylmalonyl-CoA => deoxyerythronolide B => erythromycin A/B
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01052 Type I polyketide structures
    K14370  eryK, CYP113A; erythromycin 12 hydroxylase
   00522 Biosynthesis of 12-, 14- and 16-membered macrolides
    K14370  eryK, CYP113A; erythromycin 12 hydroxylase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01008 Polyketide biosynthesis proteins
    K14370  eryK, CYP113A; erythromycin 12 hydroxylase
   00199 Cytochrome P450
    K14370  eryK, CYP113A; erythromycin 12 hydroxylase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.13  With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.13.154  erythromycin 12-hydroxylase
     K14370  eryK, CYP113A; erythromycin 12 hydroxylase
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide tailoring proteins
  Oxygenase
   K14370  eryK, CYP113A; erythromycin 12 hydroxylase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, bacteria type
  CYP113 family
   K14370  eryK, CYP113A; erythromycin 12 hydroxylase
BRITE hierarchy
Other DBs
RN: R05521 R05522
COG: COG2124
Genes
AER: AERYTH_15860
SEN: SACE_0713(eryK)
AEY: CDG81_13225
TaxonomyKoalaUniProt
Reference
  Authors
Savino C, Montemiglio LC, Sciara G, Miele AE, Kendrew SG, Jemth P, Gianni S, Vallone B
  Title
Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate.
  Journal
J Biol Chem 284:29170-9 (2009)
DOI:10.1074/jbc.M109.003590
  Sequence
[sen:SACE_0713]
Reference
PMID:8416893
  Authors
Stassi D, Donadio S, Staver MJ, Katz L
  Title
Identification of a Saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis.
  Journal
J Bacteriol 175:182-9 (1993)
DOI:10.1128/JB.175.1.182-189.1993
  Sequence
[sen:SACE_0713]

KEGG   ENZYME: 1.14.13.154Help
Entry
EC 1.14.13.154              Enzyme                                 

Name
erythromycin 12-hydroxylase;
EryK
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
erythromycin-D,NADPH:oxygen oxidoreductase (12-hydroxylating)
Reaction(IUBMB)
erythromycin D + NADPH + H+ + O2 = erythromycin C + NADP+ + H2O [RN:R05522]
Reaction(KEGG)
R05522;
(other) R05521
Show
Substrate
erythromycin D [CPD:C06633];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007]
Product
erythromycin C [CPD:C06616];
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
The enzyme is responsible for the C-12 hydroxylation of the macrolactone ring, one of the last steps in erythromycin biosynthesis. It shows 1200-1900-fold preference for erythromycin D over the alternative substrate erythromycin B [1].
History
EC 1.14.13.154 created 2012
Pathway
ec00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K14370  erythromycin 12 hydroxylase
Genes
AER: AERYTH_15860
SEN: SACE_0713(eryK)
AEY: CDG81_13225
Taxonomy
Reference
1  [PMID:7849045]
  Authors
Lambalot RH, Cane DE, Aparicio JJ, Katz L
  Title
Overproduction and characterization of the erythromycin C-12 hydroxylase, EryK.
  Journal
Biochemistry 34:1858-66 (1995)
  Sequence
[sen:SACE_0713]
Reference
2  [PMID:19625248]
  Authors
Savino C, Montemiglio LC, Sciara G, Miele AE, Kendrew SG, Jemth P, Gianni S, Vallone B.
  Title
Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate.
  Journal
J Biol Chem 284:29170-9 (2009)
DOI:10.1074/jbc.M109.003590
  Sequence
[sen:SACE_0713]
Reference
3  [PMID:20845962]
  Authors
Montemiglio LC, Gianni S, Vallone B, Savino C
  Title
Azole drugs trap cytochrome P450 EryK in alternative conformational states.
  Journal
Biochemistry 49:9199-206 (2010)
DOI:10.1021/bi101062v
  Sequence
[sen:SACE_0713]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.13.154
IUBMB Enzyme Nomenclature: 1.14.13.154
ExPASy - ENZYME nomenclature database: 1.14.13.154
BRENDA, the Enzyme Database: 1.14.13.154

KEGG   REACTION: R05521Help
Entry
R05521                      Reaction                               

Name
erythromycin-B,NADPH:oxygen oxidoreductase (12-hydroxylating)
Definition
Erythromycin B + NADPH + H+ + Oxygen <=> Erythromycin + NADP+ + H2O
Equation
Comment
1200-1900-fold preference for erythromycin D over the alternative substrate erythromycin B
Reaction class
RC00001  C00005_C00006
RC01892  C01912_C06653
Enzyme
Pathway
rn00522  Biosynthesis of 12-, 14- and 16-membered macrolides
rn01130  Biosynthesis of antibiotics
Orthology
K14370  erythromycin 12 hydroxylase [EC:1.14.13.154]

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