Production of the antitumor drug epirubicin (4'-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius

Nature Biotechnology

Volumn 16, Issue 1, 1998, Pages 69-74

  Madduri, Krishnamurthy ^a   Kennedy, Jonathan ^a   Rivola, Giovanni ^b   Inventi Solari, Augusto ^b   Filippini, Silvia ^b   Zanuso, Giovanna ^b   Colombo, Anna Luisa ^b   Gewain, Keith M ^c   Occi, James L ^c   MacNeil, Douglas J ^c   Hutchinson, C Richard ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b Technical Operations   (Italy)

^c MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Antibiotics; Fermentation; Metabolic engineering

Indexed keywords

DAUNORUBICIN; DAUNOSAMINE; DEOXYSUGAR; DOXORUBICIN; EPIRUBICIN;

ANTIBIOTIC BIOSYNTHESIS; ARTICLE; DRUG SYNTHESIS; FERMENTATION; GENE INSERTION; GENETIC ENGINEERING; NONHUMAN; PRIORITY JOURNAL; SACCHAROPOLYSPORA; STREPTOMYCES;

ANTIBIOTICS, ANTINEOPLASTIC; DNA PRIMERS; EPIRUBICIN; FERMENTATION; GENE EXPRESSION REGULATION, BACTERIAL; GENES, BACTERIAL; GENETIC ENGINEERING; GENOTYPE; HEXOSAMINES; MUTATION; PLASMIDS; PRODRUGS; STREPTOMYCES;

ACTINOBACTERIA (CLASS); BACTERIA (MICROORGANISMS); SACCHAROPOLYSPORA; STREPTOMYCES AVERMITILIS; STREPTOMYCES PEUCETIUS; UNCULTURED ACTINOMYCETE;

EID: 0031974553     PISSN: 10870156     EISSN: None     Source Type: Journal    
DOI: 10.1038/nbt0198-69     Document Type: Article

References (43)

1. Service, R.F. 1995. Antibiotics that resist resistance. Science 270:724-727.
2. McAlpine, J.B., Tuan, J.S., Brown, D.P., Grebner, K.D., Whittern, D.N., Buko, A., and Katz, L. 1987. New antibiotics from genetically engineerd actinomycetes. I. 2-Norerythromycins, isolation and structural determination. J. Antibiotics 40:1115-1122.
3. Weber, J.M., Leung, J.O., Swanson. S.J., Idler, K.B. and McAlpine, J.B. 1991. An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Science 252:114-117.
4. Donadio, S., McAlpine, J.B., Sheldon, P.J., Jackson, M., and Katz, L. 1993. An erythromycin analog produced by reprogramming of polyketide synthesis. Proc. Natl. Acad. Sci. USA 90:7119-7123.
5. Jacobsen, J.R., Hutchinson, C.R., Cane, D.E., and Khosla, C. 1997. Precursor directed biosynthesis of novel erythromycin analogs by an engineered polyketide synthase. Science 277:367-369.
6. Stachless, T., Schneider, A., and Marahiel, M.A. 1995. Rational design of peptide antibiotics by targeted replacement of bacterial and fungal domains. Science 269:69-72.
7. Epp, J., Huber, M.LB., Turner, J.R., Goodson, T., and Schoner, B.E. 1989. Production of a hybrid macrolide antibiotics in Streptomyces ambofaciens and Streptomyces lividans by introduction of a cloned carbomycin biosynthetic gene from Streptomyces thermotolerans. Gene 85:293-301.
8. Hara, O. and Hutchinson, C.R. 1992. A macrolide 3-0-acyltransferase gene from the midecamycin-producing species of Streptomyces mycarofaciens. J. Bacteriol. 174:5141-5144.
9. Arisawa, A., Kawamura, N., Takeda, K., Tsunekawa, H., Okamura, K., and Okamoto, R. 1994. Cloning of the macrolide antibiosynthesis gene acyA, which encodes 3-O-acyltransferase, from Streptomyces thermotolerans and Its use for direct fermentative production of a hybrid macrolide antibiotic. Appl. Environ. Microbiol. 60:2657-2660.
10. Hutchinson, C.R. and Ikeda, I. 1995. Polyketide synthase gene manipulation: A structure-function approach in engineering novel antibiotics. Annu. Rev. Microbiol. 49:201-238.
11. Hutchinson, C.R. 1997. Antibiotics from genetically engineered microorganisms. pp. 683-702 in Biotechnology of industrial antibiotics, 2nd ed. Strohl, W.R. (ed.). Marcel Dekker, New York.
12. Khosla, C. and Zawada, R.J.X. 1996. Generation of polyketide libraries via combinatorial biosynthesis. Trends Biotech. 14:335-341.
13. Arcamone, F., Penco, S., Vigevani, A., Redaelli, S., Franchi, G., Di Marco, A., et al. 1975. Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone. J. Med. Chem. 18:703-707.
14. Weiss, R.B. 1992. The anthracyclines: Will we ever find a better doxorubicin? Semin. Oncol. 19:670-686.
15. Suarato, A., Penco, S., and Arcamone, F. 1982. Process for the preparation of 4′-epidaunorubicin, 3′,4′-diepidaunorubicin, their doxorubicin analogs, and intermediates used in said process. US Pat. 4,345,068.
16. Madduri, K. and Hutchinson, C.R. 1995. Functional characterization and transcriptional analysis of the dnrR, locus that controls daunorubicin biosynthesis in Streptomyces peucetius. J. Bacteriol. 177:1208-1215.
17. Otten, S.L., Liu, X., Ferguson, J., and Hutchinson, C.R. 1995. Cloning and characterization of the Streptomyces peucetius dnrQS genes encoding a daunosamine biosynthesis enzyme and a glycosyl transferase involved in daunorubicin biosynthesis. J. Bacteriol. 177:6688-6692.
18. Scotti, C. and Hutchinson, C.R. 1996. Enhanced antibiotic production by manipulation of the Streptomyces peucetius dnrH and dnrT genes involved in doxorubicin (adriamycin) biosynthesis. J. Bacteriol. 178:7316-7321.
19. Otten, S.L., Gallo, M.A., Madduri, K., Liu, X., and Hutchinson, C.R. 1997. Cloning and characterization of the Streptomyces peucetius dnmZUV genes encoding three enzymes required for the biosynthesis of the daunorubicin precursor, thymidine diphospho-L-daunosamine. J. Bacteriol. 179:7316-7321.
20. Gallo, M.A., Ward, J., and Hutchinson, C.R. 1995. The dnrM gene in Streptomyces peucetius contains a naturally-occuring frameshift mutation that is suppressed by another locus outside of the daunorubicin-production gene cluster. Microbiology 142:269-275.
21. Liu, H-W. and Thorson, J.S. 1994. Pathways and mechanisms in the biogenesis of novel deoxysugars by bacteria. Annu. Rev. Microbiol. 48:223-256.
22. Katz, L. and Donadio, S. 1995. Macrolides. pp. 385-420 in Genetics and biochemistry of antibiotic production. Vining, L.C. and Stuttard, C. (eds.). Butterworth-Heinemann, Boston.
23. MacNeil, D.J. 1995. Avermectins. pp. 421-442 in Genetics and biochemistry of antibiotic production. Vining, L.C. and Stuttard, C. (eds.). Butterworth-Heinemann, Boston.
24. Summers, R.G., Donadio, S., Staver, M., Wendt-Pienkowski, E., Hutchinson, C. R., and Katz, L. 1997. Characterization of ten genes from the erythromycin gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine biosynthesis. Microbiology 143:3251-3262.
25. Occi, J.L., Gerwain, K.M., Ruby, C.L., and MacNeil, D.J. 1991. Abstracts of the annual meeting of the society for industrial microbiology, P49, p. 93. Philadelphia, PA.
26. Jiang, X.-M., Neal, B., Santiago, F., Lee, S.J., Romana, L.K., and Reeves, P.R. 1991. Structure and sequence of the rfb (O antigen) gene cluster of Salmonella serovar typhimurium (strain LT2). Mol. Microbiol. 5:695-713.
27. Macpherson, D.F., Manning, P.A., and Morona, R. 1994. Characterization of the dTDP-rhamnose biosynthetic genes encoded in the rfb locus of Shigella flexneri. Mol. Microbiol. 11:281-292.
28. Vara, J., Lewandowska-Skarbek, M., Wang, Y.-G., Donadio, S., and Hutchinson, C.R. 1989. Cloning of genes governing the deoxysugar portion of the erythromycin biosynthetic pathway in Saccharopolyspora erythraea (Streptomyces erythreus). J. Bacteriol. 171:5872-5881.
29. Bibb, M.J., White, J., Ward, J.M., and Janssen, G.R. 1994. The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site. Mol. Microbiol. 14:533-545.
30. Tagliavini, F., McArthur, R.A., Canciani, B., Giaccone, G., Porro, M., Bugiani, M., et al. 1997. Effectiveness of anthracycline against experimental prion disease in syrian hamsters. Science 276:1119-1122.
31. Dingerdissen, J.J., Sitrin, R.D., DePhillips, P.A., Gionenella, A.J., Grappel, S.F., Mehta, R.J., et al. 1987. Actinoidin A2, a novel glycopeptide: Production, preparative HPLC separation and characterization. J. Antibiotics 40:165-172.
32. Lomovskaya, N., Filippini, S., Fonstein, L., Hutchinson, C.R., and Colombo, A.L. 1997. Process for preparing doxorubicin. US patent applied for.
33. Inventi-Scolari, A., Breme, U., Colombo, A.L., Hutchinson, C.R., Otten, S., and Scotti, C. 1996. Process for preparing doxorubicin. WO 96/27014, Sept. 6, 1996.
34. Kurihara, K., Ajito, K., Shibahara, S., Ishizuka, T., Hara, O., Araake, M., and Omoto, S. 1996. Cladinose analogoues of sixteen-membered macrolide antibiotics. I. Synthesis of 4-0-alkyl-L-cladinose analogues via glycosylation. J. Antibiotics 40:582-592.
35. Solenberg, P.J., Matsushima, P., Stack, D.R. Wilkie, S.C., Thompson, R.C., and Baltz, R.H. 1997. Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem. Biol. 4:195-202.
36. Yanisch-Perron, C., Vieira, J., and Messing, J. 1985. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33:103-119.
37. Sambrook, J., Frisch, E.F. and Maniatis, T. 1989. Molecular cloning. A laboratory manual, Vols. 1 to 3. Cold Spring Harbor Press, Cold Spring Harbor, New York.
38. Hopwood, D.A, Bibb, M.J., Chater, K.F., Kieser, T., Bruton, C.J., Kieser, H.M., et al. 1985. Genetic manipulation of Streptomyces: A laboratory manual. The John Innes Foundation, Norwich. UK.
39. Guilfoile, P.G. and Hutchinson, C.R. 1991. A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. Proc. Natl. Acad. Sci. USA 88:8553-8557.
40. Meurer, G. and Hutchinson, C.R. 1995. Functional analysis of putative β-ketoa-cyl:acyl carrier protein synthase and acyltransferase active-slte-motifs in a type II polyketide synthase of Streptomyces glaucescens. J. Bacteriol. 177:477-481.
41. Hillemann, D., Puhler, A., and Wohlleben, W. 1991. Gene disruption and gene replacement in Streptomyces via single stranded DNA transformation of integration vectors. Nucl. Acids Res. 19:727-731.
42. Strohl, W.R. 1992. Compilation and analysis of DNA sequences associated with apparent streptomycetes promoters. Nucl. Acids Res. 20:961-974.
43. Devereux, J., Haeberli, P., and Smithies, O. 1984. A comprehensive set of sequence analysis programs for the VAX. Nucl. Acids Res. 12:387-395.