Claims
- 1. A method for introducing one or more hydroxyl groups or an epoxide into a polyketide, which method comprises expressing a recombinant gene encoding a P450 monoxygenase in a host cell.
- 2. The method of claim 1, wherein said P450 monooxygenase is not naturally expressed by the host cell.
- 3. The method of claim 2, wherein said polyketide is not naturally produced by the host cell.
- 4. The method of claim 1, wherein said host cell is a Streptomyces host cell.
- 5. The method of claim 1, wherein said P450 monooxygenase is OleP.
- 6. The method of claim 3, wherein said polyketide is produced by a 6-deoxyerythronolide B synthase.
- 7. The method of claim 3, wherein said polyketide is produced by a 8,8a-deoxyoleandolide synthase.
- 8. The method of claim 6, wherein a hydroxyl group is introduced at carbon 8 or 8a.
- 9. The method of claim 7, wherein a hydroxyl group is introduced at carbon 8 or 8a.
- 10. The method of claim 8, wherein 8,8a-dihydroxy-6-deoxyerythonolide B is produced.
- 11. The method of claim 8, wherein 8,8a-dihydroxyoleandolide is produced.
- 12. The method of claim 10, said method comprising culturing a host cell other than Streptomyces antibioticus that expresses DEBS and OleP under conditions such that 8,8a-dihydroxy-6-deoxyerythonolide B is produced.
- 13. The method of claim 11, said method comprising culturing a host cell other than Streptomyces antibioticus that expresses DEBS and OleP under conditions such that 8,8a-dihydroxyoleandolide is produced.
- 14. The method of claim 12, wherein said host cell is a Streptomyces host cell.
- 15. The method of claim 13, wherein said host cell is a Streptomyces host cell.
- 16. The method of claim 14, wherein said host cell is S. lividans.
- 17. The method of claim 15, wherein said host cell is S. lividans.
- 18. A compound selected from the group consisting of 8-hydroxy-6-deoxyerythronolide B, 8a-hydroxy-6-deoxyerythronolide B, 8-hydroxy-8,8a-deoxyoleandolide, 8a-hydroxy-8,8a-deoxyoleandolide, 8,8a-dihdroxy-6-deoxyerythronloide B, 8,8a-dihydroxyoleandolide, 8,8a-dehydro-6-deoxyerythronolide B, and 8,8a-anhydrooleandolide.
- 19. The compound of claim 18 that is 8,8a-dihdroxy-6-deoxyerythronloide B.
- 20. The compound of claim 19 in substantially pure form.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to PCT patent application No. 99/24478, filed Oct. 22, 1999; U.S. patent application Ser. No. 09/428,517, filed Oct. 28, 1999; U.S. provisional application Serial Nos. 60/177,660, filed Jan. 27, 2000, 60/120,254, filed Feb. 16, 1999, and 60/106,100, filed Oct. 29, 1998, each of which is incorporated herein by reference.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60177660 |
Jan 2000 |
US |
|
60120254 |
Feb 1999 |
US |
|
60106100 |
Oct 1998 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09768927 |
Jan 2001 |
US |
Child |
09991448 |
Nov 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09428517 |
Oct 1999 |
US |
Child |
09991448 |
Nov 2001 |
US |