KEGG   ORTHOLOGY: K15955Help
Entry
K15955                      KO                                     

Name
doxA, CYP129A
Definition
13-deoxydaunorubicin hydroxylase [EC:1.14.13.181]
Pathway
ko01057  Biosynthesis of type II polyketide products
ko01130  Biosynthesis of antibiotics
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01057 Biosynthesis of type II polyketide products
    K15955  doxA, CYP129A; 13-deoxydaunorubicin hydroxylase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   00199 Cytochrome P450
    K15955  doxA, CYP129A; 13-deoxydaunorubicin 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
    1.14.13.181  13-deoxydaunorubicin hydroxylase
     K15955  doxA, CYP129A; 13-deoxydaunorubicin hydroxylase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, bacteria type
  CYP129 family
   K15955  doxA, CYP129A; 13-deoxydaunorubicin hydroxylase
BRITE hierarchy
Other DBs
RN: R06688 R06689 R06690 R06691 R06692
COG: COG2124
Genes
AG: AAB08049(doxA) AAD04715(doxA)
TaxonomyKoalaUniProt
Reference
  Authors
Hertweck C, Luzhetskyy A, Rebets Y, Bechthold A
  Title
Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork.
  Journal
Nat Prod Rep 24:162-90 (2007)
DOI:10.1039/b507395m
Reference
PMID:9864344
  Authors
Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR
  Title
Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene.
  Journal
J Bacteriol 181:305-18 (1999)
  Sequence
Reference
PMID:9098063
  Authors
Dickens ML, Priestley ND, Strohl WR
  Title
In vivo and in vitro bioconversion of epsilon-rhodomycinone glycoside to doxorubicin: functions of DauP, DauK, and DoxA.
  Journal
J Bacteriol 179:2641-50 (1997)
DOI:10.1128/JB.179.8.2641-2650.1997
  Sequence

KEGG   ENZYME: 1.14.13.181Help
Entry
EC 1.14.13.181              Enzyme                                 

Name
13-deoxydaunorubicin hydroxylase;
DoxA
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
13-deoxydaunorubicin,NADPH:oxygen oxidoreductase (13-hydroxylating)
Reaction(IUBMB)
(1) 13-deoxydaunorubicin + NADPH + H+ + O2 = 13-dihydrodaunorubicin + NADP+ + H2O [RN:R06688];
(2) 13-dihydrodaunorubicin + NADPH + H+ + O2 = daunorubicin + NADP+ + 2 H2O [RN:R06689]
Reaction(KEGG)
Substrate
13-deoxydaunorubicin [CPD:C12429];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007];
13-dihydrodaunorubicin [CPD:C12430]
Product
13-dihydrodaunorubicin [CPD:C12430];
NADP+ [CPD:C00006];
H2O [CPD:C00001];
daunorubicin [CPD:C01907]
Comment
The enzymes from the Gram-positive bacteria Streptomyces sp. C5 and Streptomyces peucetius show broad substrate specificity for structures based on an anthracycline aglycone, but have a strong preference for 4-methoxy anthracycline intermediates (13-deoxydaunorubicin and 13-dihydrodaunorubicin) over their 4-hydroxy analogues (13-deoxycarminomycin and 13-dihydrocarminomycin), as well as a preference for substrates hydroxylated at the C-13 rather than the C-14 position.
History
EC 1.14.13.181 created 2013
Pathway
ec01057  Biosynthesis of type II polyketide products
ec01130  Biosynthesis of antibiotics
Orthology
K15955  13-deoxydaunorubicin hydroxylase
Reference
1  [PMID:9864343]
  Authors
Walczak RJ, Dickens ML, Priestley ND, Strohl WR
  Title
Purification, properties, and characterization of recombinant Streptomyces sp. strain C5 DoxA, a cytochrome P-450 catalyzing multiple steps in doxorubicin biosynthesis.
  Journal
J Bacteriol 181:298-304 (1999)
  Sequence
Reference
2  [PMID:9098063]
  Authors
Dickens ML, Priestley ND, Strohl WR.
  Title
In vivo and in vitro bioconversion of epsilon-rhodomycinone glycoside to doxorubicin: functions of DauP, DauK, and DoxA.
  Journal
J Bacteriol 179:2641-50 (1997)
DOI:10.1128/JB.179.8.2641-2650.1997
  Sequence
Other DBs
ExplorEnz - The Enzyme Database: 1.14.13.181
IUBMB Enzyme Nomenclature: 1.14.13.181
ExPASy - ENZYME nomenclature database: 1.14.13.181
BRENDA, the Enzyme Database: 1.14.13.181

KEGG   REACTION: R06688Help
Entry
R06688                      Reaction                               

Name
13-deoxydaunorubicin,NADPH:oxygen oxidoreductase (13-hydroxylating)
Definition
13-Deoxydaunorubicin + NADPH + H+ + Oxygen <=> 13-Dihydrodaunorubicin + NADP+ + H2O
Equation
Reaction class
RC00001  C00005_C00006
RC01674  C12429_C12430
Enzyme
Pathway
rn01057  Biosynthesis of type II polyketide products
rn01130  Biosynthesis of antibiotics
Orthology
K15955  13-deoxydaunorubicin hydroxylase [EC:1.14.13.181]
Other DBs
RHEA: 37854

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