Methods of producing doxorubicin

Details Methods of producing doxorubicin Methods of producing doxorubicin

1996-05-24

1999-11-02

Wax, Robert A.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

4351723, 435189, 4352523, 43525233, 43525235, 4353201, 435 78, 536 232, 536 237, 536 231, C12P 100, C07H 2104

Patent

active

059768304

ABSTRACT:
The present invention provides novel methods for producing doxorubicin using daunomycin as a substrate. One method employs a genetically engineered host microorganism which is transformed with a vector, preferably a plasmid, which contains the doxA gene. Preferably, the doxA gene, also referred to herein as "doxA", is cloned into a plasmid which is then introduced into the host microorganism, preferably a bacterial host, more preferably Streptomyces, to provide a transformed host microorganism. The doxA gene, when present on a plasmid, confers on the transformed host the ability to convert daunomycin and 13-dihydrodaunomycin, to doxorubicin. The doxA gene encodes a P450-like enzyme which catalyzes the hydroxylation of daunomycin and 13-dihydrodaunomycin at C-14 to form doxorubicin; such enzyme is designated "daunomycin C-14 hydroxylase". Thus, the expression of doxA in the transformed host using a plasmid which contains doxA enables the transformed host to convert daunomycin to doxorubicin. The doxorubicin is then extracted from host microorganism cultures.

REFERENCES:
patent: 5008380 (1991-04-01), Palladino et al.
patent: 5695966 (1997-12-01), Inventi et al.
one page computer print-out of search identifying WO 9627014, "New DNA Encoding Daunorubicin 14-hydroxylase", Sep. 6, 1996 and containing abstract of application.
"Adriamycin, 14-Hydroxydaunomycin, a New Antitumor Antibiotic from S.peuceilus var. caesius" by Arcamone, et al., Biotechnology and Bioengineering, vol. XI, pp. 1101-1110 (1969).
"Cloning of genetic loci involved in endoprotease activity in Streptomyces lividans 66:" by Butler, et al., Can. J. Microbiol., vol. 38, 912-201 1992.
"Biosynthetic relationships amoung daunorubicin, doxorubicin and 13-dihydrodaunorubicin", by Crespi-Perellino, et al., Esperientia 38 (1982), Birkhauser Verlag, CH-4010 Basel-Switzerland.
"A metalloprotease gene from Streptomyces coelicolor `Muller` an its transcriptional activator" by Dammann, et al., Molecular Microbiology, (1992) 6(16) pp. 2267-2278.
"Isolation and Characterization of a Gene from Streptomyces sp. Strain C5 that Confers the Ability to Convert Daunmycin to Doxorubicon on Streptomyces lividans TK24" by Dickens, et al., J. of Bacteriology, Jun. 1996, pp. 3389-3395.
"Cloning, Sequencing, and Analysis of Aklaviketone Reductase from Streptomyces sp. Strain C5" by Dickens, et al., J. of Bacteriology, Jun. 1996, pp. 3384-3388.
"Biosynthesis of Anthracyclines in Streptomyces Peucetius" by Grein, et al. Sixth Int. Symp. on Actinomycetes Biology, 1985, pp. 263-266.
"Anthacyclines", Chapter 12 of Genetics and Biochemistry of Antibiotic Production, edited by Leo C. Vining and Colin Stuttard.
"Cloning and Sequencing of a Gene Encoding a Novel Extracellular Neutral Proteinase . . . " by Lampel, et al., J. of Bacteriology, May 1992, vol. 174, No. 9, pp. 2797-2808.
"Cloning and characterization of a gene encoding extracellular metalloprotease . . . " by Lichenstein, et al., Gene, 111 (1992) pp. 125-130.
"Microbial Metabolism of Anthracycline Antiobiotics Daunomycin and Adriamycin" by Marshall, et al., Journal of Antibiotics, Apr. 1978, pp. 336-342.
"Biosynthesis of Daunorubicin Glycosides", Antimicrobial Agents and Chemotherapy, Sep. 1980, vol. 18, No. 3, pp. 454-464.
"Microbial Conversion of Daunomycin, Carminomycin I and Feudomycin A to Adriamycin" Journal of Antiobiotics, Sep. 1981, vol. XXXIV, No. 9, pp. 1229-1231.
"Cloning and Expression of Daunorubicin Biosynthesis Genes from Streptomyces peucetius . . . " by Otten, et al., J. of Bacteriology, Jun. 1990, vol. 172, No. 6, pp. 3427-3434.
"Identification of a Saccharopolyspora erythraea Gene Required for the Final Hydroxylation Step . . . " by Stassi, et al., J. of Bacteriology, Jan. 1993, vol. 175, No. 1, pp. 182-189.
"Biosynthesis of Natural and Hybrid Polyketides" by Strohl, et al., Genetics and Molecular Biology of Industrial Microorganisms, 1989 Am. Soc. for Microbiology, Washington, D.C., pp. 68-84.
"Daunorubicin and Adriamycin: Properties, Biosynthesis, and Fermentation", by White, et al., Biotechnology of Industrial Antiobiotics, 1984, pp. 569-594.
"Isolation and Sequence Analysis of Polyketide Synthase Genes from the Daunomycin-Producing Streptomyces sp. Strain C5", by Ye, et al., J. of Bacteriology, vol. 176, No. 20, Oct. 1994, pp. 6270-6280.
"Characterization of Saccharopolyspora erythraea Cytochrome P-450 Genes and Enzymes . . . " by Andersen, et al., J. of Bacteriology, Feb. 1992, vol. 174, No. 3, pp. 725-735.

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