KEGG ENZYME: 1.14.13.181

ENZYME: 1.14.13.181

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

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)

R06688 R06689;
(other) R06690 R06691 R06692

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

ec01110

Biosynthesis of secondary metabolites

Orthology

K15955

13-deoxydaunorubicin hydroxylase

Genes

SPEU:

CGZ69_24370

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)
DOI:10.1128/JB.181.1.298-304.1999

Sequence

[ag:AAB08049]

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