Genetically modified strains producing anthracycline metabolites useful as cancer drugs

1 . A microbial strain that produces anthracycline metabolites at a titre of at least 0.5 g/l fermentation broth.

2 . The strain according to claim 1 , which produces at least 0.1 g/l fermentation broth of each of the compounds epidaunorubicin, 13-dihydro-epidaunorubicin, 4′-epi-feudomycin and ε-rhodomycinone.

3 . The strain according to claim 1 , which produces at least one of the compounds epidaunorubicin, 13-dihydro-epidaunorubicin, 4′-epi-feudomycin and ε-rhodomycinone in at least 10% of the total anthracycline metabolite fraction.

4 . The strain according to claim 1 , wherein the biosynthesis of endogeneous daunomycin metabolites is blocked.

5 . The strain according to claim 4 , wherein baumycin production is blocked by random mutagenization.

6 . The strain according to claim 1 , which carries genes for 4′ketoreductase and for O-methylation.

7 . The strain according to claim 6 , wherein said genes are ekr8 and rdmB.

8 . The strain according to claim 1 , wherein said strain is selected from the genera Streptomyces.

9 . The strain according to claim 8 , wherein said strain is selected from the species Streptomyces peucetius.

10 . The strain according to claim 9 , wherein said strain is selected from the species Streptomyces peucetius var. caesius.

11 . A process for producing anthracycline metabolites comprising fermenting a microbial producer strain according to claim 1 .

12 . The process according to claim 11 , wherein said anthracycline metabolites are selected from the group consisting of epidaunomycins and ε-rhodomycinone.

13 . The process according to claim 12 , wherein said anthracycline metabolites are selected from the group consisting of epidaunorubicin, 13-dihydroepidaunorubicin, 4′-epi-feudomcyin and ε-rhodomycinone.

14 . The process according to claim 1 , which further comprises absorbing crude epidaunomycins and ε-rhodomycinone from the fermentation broth by adding a resin at any time.

15 . The process according to claim 14 , wherein said resin is selected from the group consisting of ionic and non-ionic adsorbents.

16 . The process according to claim 15 , wherein said resin is selected from the group consisting of polystyrenes.

17 . The process according to claim 16 , wherein said resin is selected from the group consisting of XAD-7 and Diaion HP-20.

18 . The process according to claim 14 , which further comprises addine said resin in an amount of 1-100 g/l.

19 . The process according to claim 18 , which further comprises adding said resin in an amount of 15-40 g/l.