Erythromycin 12 hydroxylase

Erythromycin 12 hydroxylase
Identifiers
EC no.1.14.13.154
Databases
BRENDAenzyme data
ExPASyNiceZyme view
KEGGenzyme entry
MetaCycmetabolic pathway
Rheareactions
PDB structuresRCSB PDB PDBe PDBsum
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NCBIproteins

Erythromycin 12 hydroxylase (EC 1.14.13.154, EryK) is an enzyme with systematic name erythromycin-D,NADPH:oxygen oxidoreductase (12-hydroxylating) .[1][2][3] This enzyme catalyses the following chemical reaction

2D representation of the chemical structure of Q27103642.
erythromycin D
+ NADPH
+ H+
 
 
O2
H2O
Rightward reaction arrow with minor substrate(s) from top left and minor product(s) to top right
 
 
 
2D representation of the chemical structure of Q27133183.
erythromycin C
 

The enzyme characterised from Saccharopolyspora erythraea converts erythromycin D into erythromycin C by introduction of a hydroxy group at the C-12 position of the macrocycle. It uses reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen as cofactors.[4] Erythromycin C is subsequently converted to the antibiotic, erythromycin A, by the enzyme erythromycin 3''-O-methyltransferase.[5]

References

  1. ↑ Lambalot RH, Cane DE, Aparicio JJ, Katz L (February 1995). "Overproduction and characterization of the erythromycin C-12 hydroxylase, EryK". Biochemistry. 34 (6): 1858–66. doi:10.1021/bi00006a006. PMID 7849045.
  2. ↑ Savino C, Montemiglio LC, Sciara G, Miele AE, Kendrew SG, Jemth P, Gianni S, Vallone B (October 2009). "Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate". The Journal of Biological Chemistry. 284 (42): 29170–9. doi:10.1074/jbc.M109.003590. PMC 2781461. PMID 19625248.
  3. ↑ Montemiglio LC, Gianni S, Vallone B, Savino C (November 2010). "Azole drugs trap cytochrome P450 EryK in alternative conformational states". Biochemistry. 49 (43): 9199–206. doi:10.1021/bi101062v. PMID 20845962.
  4. ↑ Enzyme 1.14.13.154 at KEGG Pathway Database.
  5. ↑ Summers RG, Donadio S, Staver MJ, Wendt-Pienkowski E, Hutchinson CR, Katz L (October 1997). "Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production". Microbiology. 143 (10): 3251–62. doi:10.1099/00221287-143-10-3251. PMID 9353926.