Claims
- 1. A process for producing avermectins comprising culturing cells of a strain of Streptomyces avermitilis which express a mutated aveC allele, wherein said mutated aveC allele encodes a gene product that reduces a ratio of class 2 avermectins to class 1 avermectins when compared to cells of the same strain which express only the wild-type aveC allele, wherein said cells are placed in culture media under conditions that permit or induce the production of avermectins therefrom, and recovering said avermectins from the culture.
- 2. The process of claim 1, wherein the class 2:1 avermectins are cyclohexyl-B2:cyclohexyl-B1 avermectins.
- 3. The process of claim 2, wherein the reduced ratio of cyclohexyl-B2:cyclohexyl-B1 avermectins is up to 1.6:1.
- 4. The process of claim 2, wherein the reduced ratio of cyclohexyl -B2:cyclohexyl-B1 avermectins is up to 1:1.
- 5. The process of claim 4, wherein the reduced ratio of cyclohexyl-B2:cyclohexyl-B1 avermectins is up to 0.94:1.
- 6. The process of claim 2, wherein the reduced ratio of cyclohexyl-B2:cyclohexyl-B1 avermectins is up to 0.88:1.
- 7. The process of claim 6, wherein the reduced ratio of cyclohexyl-B2:cyclohexyl-B1 avermectins is 0.88:1.
- 8. The process of claim 6, wherein the reduced ratio of cyclohexyl-B2:cyclohexyl-B1 avermectins is 0.84:1.
- 9. The process of claim 2, wherein the mutation to the aveC allele encodes an amino acid substitution at residue 139 from alanine to threonine, or at residue 138 from serine to threonine, or at both residue 138 from serine to threonine and at residue 139 from alanine to threonine; which amino acid positions are of reference SEQ ID NO:2.
- 10. The process of claim 2, wherein the reduced ratio of cyclohexyl-B2:cyclohexyl-B1 vermectins is 0.75:1.
- 11. A process of claim 2, wherein the mutation to the S. avermetilis aveC allele encodes amino acid substitution at both residue 138 from serine to threonine and at residue 139 from alanine to phenylalanine: which amino acid positions corresponds to the amino acid position of SEQ ID NO:2.
- 12. A composition comprising culture medium and cyclohexyl-B2:cyclohexyl-B1 avermectins produced by cells of a strain of Streptomyces avermitilis, wherein said cells express a mutated aveC allele that encodes a gene product that reduces the cylohexyl-B2:cyclohexyl-B1 ratio of avermectins when compared to cells of the same strain which express only the wild-type aveC allele, wherein the cyclohexyl-B2:cyclohexyl-B1 avermectins are present in a ratio of up to 1:1.
- 13. The composition of claim 12, wherein the cyclohexyl-B2:cyclohexyl-B1 vermectins are present in the exhausted culture medium in a ratio of up to 0.84:1.
- 14. The composition of claim 12, wherein the cyclohexyl-B2:cyclohexyl-B1 avermectins are present in the exhausted culture medium in a ratio of up to 0.80:1.
- 15. The composition of claim 12, wherein the cyclohexyl-B2:cyclohexyl-B1 avermectins are present in the exhausted culture medium in a ratio of 0.94:1.
- 16. The composition of claim 12, wherein the cyclohexyl-B2:cyclohexyl-B1 avermectins are present in the exhausted culture medium in a ratio of 0.88:1.
- 17. The composition of claim 12, wherein the cyclohexyl-B2:cyclohexyl-B1 avermectins are present in the exhausted culture medium in a ratio of 0.84:1.
- 18. The composition of claim 12, wherein the cyclohexyl-B2:cyclohexyl-B1 avermectins are present in the exhausted culture medium in a ratio of 0.75:1.
Parent Case Info
This application is a divisional of U.S. application Ser. No. 09/372,934 filed Aug. 12, 1999, now U.S. Pat. No. 6,248,579, which is a continuation-in-part of PCT/IB99/00130, filed Jan. 25, 1999, which claims priority from U.S. provisional application No. 60/074,636, filed Feb. 13, 1998.
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Number |
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|
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Continuation in Parts (1)
|
Number |
Date |
Country |
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US |
Child |
09/372934 |
|
US |