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Information on EC 1.14.13.154 - erythromycin 12-hydroxylase and Organism(s) Saccharopolyspora erythraea and UniProt Accession P48635

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IUBMB Comments
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 .
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This record set is specific for:
Saccharopolyspora erythraea
UNIPROT: P48635
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Word Map
  • 1.14.13.154
  • editing
  • inosine
  • a-to-i
  • deaminases
  • deamination
  • symmetrica
  • hereditaria
  • dyschromatosis
  • rna-editing
  • rna-specific
  • adenosine-to-inosine
  • interferon-inducible
  • ifn-inducible
  • glur-b
  • site-selective
  • zalpha
  • left-handed
  • adar2-mediated
  • hypopigmented
  • dsrbds
  • recoding
  • hyperediting
  • synthesis
  • macules
  • z-dna-binding
  • genodermatosis
  • dsrna-binding
The taxonomic range for the selected organisms is: Saccharopolyspora erythraea
The enzyme appears in selected viruses and cellular organisms
Synonyms
erythromycin c-12 hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
erythromycin C-12 hydroxylase
-
SYSTEMATIC NAME
IUBMB Comments
erythromycin-D,NADPH:oxygen oxidoreductase (12-hydroxylating)
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].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
erythromycin B + NADPH + H+ + O2
erythromycin A + NADP+ + H2O
show the reaction diagram
-
1200-1900-fold preference for erythromycin D over the alternative C-12 hydroxylase substrate erythromycin B
-
-
?
erythromycin D + NADPH + H+ + O2
erythromycin C + NADP+ + H2O
show the reaction diagram
additional information
?
-
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
erythromycin D + NADPH + H+ + O2
erythromycin C + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P-450
-
cytochrome P-450
-
a heme-thiolate protein (P-450)
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
clotrimazole
induces a distortion of the internal helix I that affects the accessibility of the binding pocket by regulating the kink of the external helix G via a network of interactions that involves helix F
ketoconazole
induces a distortion of the internal helix I that affects the accessibility of the binding pocket by regulating the kink of the external helix G via a network of interactions that involves helix F
erythromycin D
-
substrate inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008
erythromycin D
-
pH 7.5, 30°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.8
erythromycin D
-
pH 7.5, 30°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
225
erythromycin D
-
pH 7.5, 30°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0166
erythromycin D
-
pH 7.5, 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
an Saccharopolyspora erythraea strain disrupted in eryK no longer produces erythromycin A but accumulates the B and D forms of the antibiotic
physiological function
the enzyme is responsible for the C-12 hydroxylation of the macrolactone ring, one of the last steps in erythromycin biosynthesis
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
43759
x * 43759, calculated from sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 43759, calculated from sequence
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of EryK in complex with the azole inhibitors ketoconazole and clotrimazole
different crystal forms are harvested from distinct crystallization conditions: two ligand-free forms, one substrate bound and two inhibitors-bound. All crystals belong either to the monoclinc P2(1)or to the orthorhombic P2(1)2(1)2(1) space groups, and exhibit diffraction limits ranging from 2.3 to 1.6 A
vapor diffusion at 21°C, three crystal forms of EryK are obtained in different crystallization conditions: with His tag (His6-EryK) in low salt conditions, without tag (EryK) in high salt, and in complex with its substrate erythromycin D (ErD-EryK)
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
recombinant His-tagged EryK is overexpressed in BL21 STAR (DE3) Escherichia coli strain
recombinant His-tagged EryK is overexpressed in the Escherichia coli BL21
overproduction of EryK in Escherichia coli as insoluble inclusion bodies
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
systematically modulating the enzyme amounts of EryK and EryG by integrating additional eryK and eryG copies into the industrial strain Saccharopolyspora erythraea HL3168 E3 significantly enhances the process of biotransformation from erythromycin-D to erythromycin-A, nearly completely eliminates the by-products erythromycin-B and erythromycin-C, and efficiently improves erythromycin-A production and purity at the fermentation stage. In conjunction with other traditional and genetic ways to continuously evaluate the erythromycin-A production system
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chen, Y.; Deng, W.; Wu, J.; Qian, J.; Chu, J.; Zhuang, Y.; Zhang, S.; Liu, W.
Genetic modulation of the overexpression of tailoring genes eryK and eryG leading to the improvement of erythromycin A purity and production in Saccharopolyspora erythraea fermentation
Appl. Environ. Microbiol.
74
1820-1828
2008
Saccharopolyspora erythraea (P48635)
Manually annotated by BRENDA team
Lambalot, R.H.; Cane, D.E., Aparicio, J.J.; Katz, L.
Overproduction and characterization of the erythromycin C-12 hydroxylase, EryK
Biochemistry
34
1858-1866
1995
Saccharopolyspora erythraea
Manually annotated by BRENDA team
Montemiglio, L.C.; Gianni, S.; Vallone, B.; Savino, C.
Azole drugs trap cytochrome P450 EryK in alternative conformational states
Biochemistry
49
9199-9206
2010
Saccharopolyspora erythraea (P48635)
Manually annotated by BRENDA team
Lee, S.K.; Basnet, D.B.; Choi, C.Y.; Sohng, J.K.; Ahn, J.S.; Yoon, Y.J.
The role of erythromycin C-12 hydroxylase, EryK, as a substitute for PikC hydroxylase in pikromycin biosynthesis
Bioorg. Chem.
32
549-559
2004
Saccharopolyspora erythraea (P48635), Saccharopolyspora erythraea
Manually annotated by BRENDA team
Stassi, D.; Donadio, S.; Staver, M.J.; Katz, L.
Identification of a Saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis
J. Bacteriol.
175
182-189
1993
Saccharopolyspora erythraea (P48635)
Manually annotated by BRENDA team
Savino, C.; Montemiglio, L.C.; Sciara, G.; Miele, A.E.; Kendrew, S.G.; Jemth, P.; Gianni, S.; Vallone, B.
Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate
J. Biol. Chem.
284
29170-29179
2009
Saccharopolyspora erythraea (P48635)
Manually annotated by BRENDA team
Savino, C.; Sciara, G.; Miele, A.E.; Kendrew, S.G., Vallone, B.
Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of C-12 hydroxylase EryK from Saccharopolyspora erythraea
Protein Pept. Lett.
15
1138-1141
2008
Saccharopolyspora erythraea (P48635), Saccharopolyspora erythraea
Manually annotated by BRENDA team