6-deoxyerythronolide B hydroxylase

Details

Name
6-deoxyerythronolide B hydroxylase
Synonyms
  • 1.14.13.188
  • 6-DEB hydroxylase
  • CYP107A1
  • CYPCVIIA1
  • Cytochrome P450 107A1
  • Cytochrome P450eryF
  • Erythromycin A biosynthesis hydroxylase
Gene Name
eryF
Organism
Saccharopolyspora erythraea (strain ATCC 11635 / DSM 40517 / JCM 4748 / NBRC 13426 / NCIMB 8594 / NRRL 2338)
Amino acid sequence
>lcl|BSEQ0011165|6-deoxyerythronolide B hydroxylase
MTTVPDLESDSFHVDWYRTYAELRETAPVTPVRFLGQDAWLVTGYDEAKAALSDLRLSSD
PKKKYPGVEVEFPAYLGFPEDVRNYFATNMGTSDPPTHTRLRKLVSQEFTVRRVEAMRPR
VEQITAELLDEVGDSGVVDIVDRFAHPLPIKVICELLGVDEKYRGEFGRWSSEILVMDPE
RAEQRGQAAREVVNFILDLVERRRTEPGDDLLSALIRVQDDDDGRLSADELTSIALVLLL
AGFEASVSLIGIGTYLLLTHPDQLALVRRDPSALPNAVEEILRYIAPPETTTRFAAEEVE
IGGVAIPQYSTVLVANGAANRDPKQFPDPHRFDVTRDTRGHLSFGQGIHFCMGRPLAKLE
GEVALRALFGRFPALSLGIDADDVVWRRSLLLRGIDHLPVRLDG
Number of residues
404
Molecular Weight
45098.685
Theoretical pI
4.69
GO Classification
Functions
heme binding / iron ion binding / monooxygenase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Processes
erythromycin biosynthetic process / oxidation-reduction process
Components
cytoplasm
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Specific Function
Catalyzes the NADPH-dependent conversion of 6-deoxyerythronolide B (6-DEB) to erythronolide B (EB) by the insertion of an oxygen at the 6S position of 6-DEB. Requires the participation of a ferredoxin and a ferredoxin reductase for the transfer of electrons from NADPH to the monooxygenase.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0011166|6-deoxyerythronolide B hydroxylase (eryF)
ATGACGACCGTTCCCGATCTCGAAAGCGACTCCTTCCACGTCGACTGGTACCGCACCTAC
GCCGAGCTGCGCGAGACCGCGCCGGTGACGCCGGTGCGCTTCCTCGGCCAGGACGCGTGG
CTGGTCACCGGCTACGACGAGGCGAAGGCCGCGCTGAGCGACCTGCGCCTGAGCAGCGAC
CCGAAGAAGAAGTACCCGGGCGTGGAGGTCGAGTTCCCGGCATACCTCGGTTTCCCCGAG
GACGTGCGGAACTACTTCGCCACCAACATGGGCACCAGCGACCCGCCGACCCACACCCGG
CTGCGCAAGCTGGTGTCGCAGGAGTTCACCGTCCGCCGCGTGGAGGCGATGCGGCCCCGC
GTCGAGCAGATCACCGCGGAGCTGCTCGACGAGGTGGGCGACTCCGGCGTGGTCGACATC
GTCGACCGCTTCGCCCACCCGCTGCCCATCAAGGTCATCTGCGAGCTGCTCGGCGTCGAC
GAGAAGTACCGCGGGGAGTTCGGGCGGTGGAGCTCGGAGATCCTGGTCATGGACCCGGAG
CGGGCCGAACAGCGCGGGCAGGCGGCCAGGGAGGTCGTCAACTTCATCCTCGACCTGGTC
GAGCGCCGCCGCACCGAGCCCGGCGACGACCTGCTGTCCGCGCTGATCAGGGTCCAGGAC
GACGATGACGGTCGGCTCAGCGCCGACGAGCTGACCTCCATCGCGCTGGTGCTGCTGCTG
GCCGGTTTCGAGGCGTCGGTGAGCCTCATCGGGATCGGCACCTACCTGCTGCTCACCCAC
CCGGACCAGCTCGCGCTGGTGCGGCGGGACCCGTCGGCGCTGCCCAACGCCGTCGAGGAG
ATCCTGCGCTACATCGCTCCGCCGGAGACCACCACGCGCTTCGCCGCGGAGGAGGTGGAG
ATCGGCGGTGTCGCGATCCCCCAGTACAGCACGGTGCTGGTCGCGAACGGCGCGGCCAAC
CGCGACCCGAAGCAGTTCCCGGACCCCCACCGCTTCGACGTCACCCGCGACACCCGCGGC
CACCTGTCGTTCGGGCAGGGCATCCACTTCTGCATGGGCCGGCCGCTGGCCAAGCTGGAG
GGCGAGGTGGCGCTGCGGGCGCTGTTCGGCCGCTTCCCCGCTCTGTCGCTGGGAATCGAC
GCCGACGACGTGGTGTGGCGGCGTTCGCTGCTGCTGCGGGGCATCGACCACCTACCGGTG
CGGCTCGACGGATGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ00441
UniProtKB Entry NameCPXJ_SACEN
GenBank Protein ID48942
GenBank Gene IDX60379
General References
  1. Haydock SF, Dowson JA, Dhillon N, Roberts GA, Cortes J, Leadlay PF: Cloning and sequence analysis of genes involved in erythromycin biosynthesis in Saccharopolyspora erythraea: sequence similarities between EryG and a family of S-adenosylmethionine-dependent methyltransferases. Mol Gen Genet. 1991 Nov;230(1-2):120-8. [Article]
  2. Weber JM, Leung JO, Swanson SJ, Idler KB, McAlpine JB: An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Science. 1991 Apr 5;252(5002):114-7. [Article]
  3. Oliynyk M, Samborskyy M, Lester JB, Mironenko T, Scott N, Dickens S, Haydock SF, Leadlay PF: Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338. Nat Biotechnol. 2007 Apr;25(4):447-53. Epub 2007 Mar 18. [Article]
  4. Andersen JF, Hutchinson CR: Characterization of Saccharopolyspora erythraea cytochrome P-450 genes and enzymes, including 6-deoxyerythronolide B hydroxylase. J Bacteriol. 1992 Feb;174(3):725-35. [Article]
  5. Cupp-Vickery JR, Poulos TL: Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat Struct Biol. 1995 Feb;2(2):144-53. [Article]
  6. Cupp-Vickery J, Anderson R, Hatziris Z: Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3050-5. [Article]
  7. Cupp-Vickery JR, Garcia C, Hofacre A, McGee-Estrada K: Ketoconazole-induced conformational changes in the active site of cytochrome P450eryF. J Mol Biol. 2001 Aug 3;311(1):101-10. [Article]
  8. Nagano S, Cupp-Vickery JR, Poulos TL: Crystal structures of the ferrous dioxygen complex of wild-type cytochrome P450eryF and its mutants, A245S and A245T: investigation of the proton transfer system in P450eryF. J Biol Chem. 2005 Jun 10;280(23):22102-7. Epub 2005 Apr 11. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01536Androstenedioneexperimental, illicitunknowninducerDetails
DB033699-AminophenanthreneexperimentalunknownDetails
DB040706-Deoxyerythronolide BexperimentalunknownDetails