Bioconversion of the anthracycline analogue desacetyladriamycin by recombinant DoxA, a P450-monooxygenase from Streptomyces sp. strain C5.
[reaction: see text] A recombinant P450-monooxygenase, DoxA, obtained from Streptomyces sp. strain C5, the producer of the anticancer compound daunorubicin, was expressed in S. lividans TK24 and therein used to catalyze the conversion of the anthracycline analogue desacetyladriamycin into the new anthracycline, 10-hydroxydesacetyladriamycin. This work establishes a new function for DoxA and demonstrates the use of a recombinant enzyme to prepare a new anthracycline analogue.
Walczak
R J
RJ
Department of Chemistry, The University of Montana, Missoula, Montana 59812, USA.
Hines
J V
JV
Strohl
W R
WR
Priestley
N D
ND
D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis / Q000378:metabolism*; D001426:Bacterial Proteins; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism*; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
C433946:10-hydroxydesacetyladriamycin; D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D011994:Recombinant Proteins; C028738:desacetyladriamycin; D004317:Doxorubicin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C116920:doxA protein, Streptomyces peucetius