GENETICALLY MODIFIED STRAINS FOR BIOTRANSFORMATIONS IN ANTHRACYCLINE PRODUCTION
A microbial strain which converts anthracycline metabolites into non-natural anthracycline antibiotics is described. A process for converting anthracycline metabolites into anthracycline antibiotics using a microbial strain is also described.
1 . A microbial strain, which converts anthracycline metabolites into non-natural anthracycline antibiotics.
2 . The strain according to claim 1 , wherein said anthracycline metabolites are selected from the group consisting of epidaunorubicin, 13-dihydroepidaunorubicin, 4′-epi-feudomcyin and ε-rhodomycinone.
3 . The strain according to claim wherein said non-natural anthracycline antibiotics are selected from the group consisting of epirubicin and idarubicin.
4 . The strain according to claim 1 , wherein said strain is selected from the genera Streptomyces.
5 . The strain according to claim 4 , wherein said strain is selected from the species Streptomyces peucetius.
6 . The strain according to claim 5 , wherein said strain is selected from the subspecies Streptomyces peucetius var. caesius.
7 . The strain according to claim 1 , comprising a heterologous resistance gene snorO.
8 . The strain according to claim 7 , wherein said gene is isolated from genus Streptomyces.
9 . The strain according to claim 8 , wherein said gene is isolated from the species Streptomyces nogalater.
10 . The strain according to claim 1 , wherein said strain provides a conversion rate of the anthracycline metabolites into the non-natural anthracycline antibiotics of >20%.
11 . The strain according to claim 10 , wherein said strain provides a conversion rate of the anthracycline metabolites into the non-natural anthracycline antibiotics of >30%.
12 . The strain according to claim 11 , wherein said strain provides a conversion rate of the anthracycline metabolites into the non-natural anthracycline antibiotics of >40%.
13 . A process for converting anthracycline metabolites into anthracycline antibiotics using a microbial strain.
14 . The process according to claim 13 , wherein said anthracycline metabolites are selected from the group consisting of epidaunorubicin, 13-dihydroepidaunorubicin, 4′-epi-feudomcyin and ε-rhodomycinone.
15 . The process according to claim 13 , wherein said anthracycline antibiotics are selected from the group consisting of epirubicin and idarubicin.
16 . The process according to claim 13 wherein said strain is selected from the genera Streptomyces.
17 . The process according to claim 16 , wherein said strain is selected from the species Streptomyces peucetius.
18 . The process according to claim 17 , wherein said strain is selected from the subspecies Streptomyces peucetius var. caesius.
19 . The process according to claim 13 , wherein said strain is genetically modified.
20 . The process according to claim 13 , wherein said strain provides a conversion rate of the anthracycline metabolites into the non-natural anthracycline antibiotics of >20%.
21 . The process according to claim 20 , wherein said strain provides a conversion rate of the anthracycline metabolites into the non-natural anthracycline antibiotics of >30%.
22 . The process according to claim 21 , wherein said strain provides a conversion rate of the anthracycline metabolites into the non-natural anthracycline antibiotics of >40%.
23 . The process according of to claim 13 , wherein purity of crude anthracycline metabolites used for biotransformation is >60%.
24 . The process according to claim 23 , wherein purity of crude anthracycline metabolites used for biotransformation is >80%.
25 . The process according to claim 24 , wherein purity of crude anthracycline metabolites used for biotransformation is >90%.
26 . The process according to claim 13 , wherein a resin is used at any time to adsorb the anthracycline metabolites or anthracycline antibiotics.
27 . The process according to claim 26 , wherein said resin is selected from the group consisting of ionic and non-ionic adsorbents.
28 . The process according to claim 27 , wherein said resin is selected from the group of polystyrenes.
29 . The process according to claim 28 , wherein said resin is selected from the group consisting of XAD-7 and Diaion HP-20.
30 . The process according to claim 26 , wherein said resin is added in an amount of 1-100 g/l.
31 . The process according to claim 30 , wherein said resin is added in an amount of 10-50 g/l.
32 . The process according to claim 31 , wherein said resin is most preferably added in an amount of 15-30 g/l.
33 . A method of using epidaunorubicin, 13-dihydroepidaunorubicin, 4′-epi-feudomycyin or ε-rhodomycinone for converting into anthracycline antibiotics comprising using a microbial strain.