Directing the ratio of B2:B1 avermectins in Streptomyces avermitilis host cells
AssigneePfizer Inc.
InventorsKim J. Stutzman-Engwall, Yan Chen, Claes Gustafsson, Anke Krebber, Jeremy Minshull, Sun Ai Raillard
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Abstract
The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding an aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of S. avermitilis. The present invention further relates to vectors, host cells, and mutant strains of S. avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.
Claims42
A method for making a novel strain of S. avermitilis, comprising mutating the aveCallele in cells of a strain of S. avermitilis, which mutation results in the substitution in the aveC gene product of a different amino acid residue at one or more amino acid positions corresponding to amino acid residues 38, 48, 89, 99, 111, 136, 154, 179, 228, 238, 289 or 298 of SEQ ID NO:2, such that cells of the S. avermitilis strain in which the aveC allele has been so mutated produce a class 2:1 ratio of avermectins that is different from the ratio produced by cells of the same S. avermitilis strain that instead express only the wild-type aveC allele.
A Streptomyces avermitilis cell having a mutated aveC allele that encodes an AveC gene product having a substitution at one or more amino acid positions corresponding to amino acid residue 38, 48, 89, 99, 111, 136, 154, 179, 228, 238, 289, or 298 of SEQ ID NO:2, wherein the cell produces a class 2:1 ratio of avermectins that is different from the ratio produced by a cell of the same S. avermitilis strain but that instead expresses only the wild-type aveC allele.
Dependencies are inferred from the claim text.