Biological production of clavulanic acid and related compounds
OwnerWei Lian, Wei-Shou Hu +1inventors
InventorsWei Lian, Wei-Shou Hu, David Sherman
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Abstract
Disruption of the two-component regulatory system encoded by the cbsA locus is associated with improved production of cephamycin C and/or clavulanic acid in Streptomyces clavuligerus.
Claims25
A genetically modified Streptomyces comprising a structural alteration in the cbsA locus that reduces or eliminates the production or activity of a gene product of either or both of cbsA1 or cbsA2, which genetically modified Streptomyces exhibits enhanced production of a bioactive metabolite compared to the level of production of the bioactive metabolite in a wild-type Streptomyces.
A method for making a bioactive metabolite comprising:
- introducing an exogenous agent into a Streptomyces to yield a modified Streptomyces, wherein the exogenous agent reduces or eliminates the production or activity of a gene product of either or both of cbsA1 or cbsA2;
- culturing the modified Streptomyces under conditions and for a time sufficient to produce the bioactive metabolite;
- and
- isolating the bioactive metabolite.
A method for making a modified Streptomyces comprising modifying a Streptomyces cell to reduce or eliminate the production or activity of a gene product of either or both of cbsA1 or cbsA2.
A genetically modified S. clavuligerus comprising a structural alteration in the cbsA locus that reduces or eliminates the production or activity of a gene product of either or both of cbsA1 or cbsA2, which genetically modified S. clavuligerus exhibits enhanced production of a cephamycin or a clavulanic acid compared to the level of production of the cephamycin or clavulanic acid in a wild-type S. clavuligerus.
A method for producing a bioactive metabolite in S. clavuligerus comprising reducing or eliminating the production or activity of an RNA or polypeptide gene product encoded by cbsA1 or cbsA2, wherein said reduction or elimination in the production of activity of the gene product results in increased production of the bioactive metabolite.
An isolated polypeptide comprising an amino acid sequence having at least 80% identity to SEQ ID NO:
- 3 or SEQ ID NO:5.
An isolated polynucleotide that encodes a polypeptide comprising an amino acid sequence having at least 80% identity to SEQ ID NO:
- 3 or SEQ ID NO:5.
An isolated polynucleotide comprising a nucleotide sequence encoding SEQ ID NO:3 or SEQ ID NO:5, or its complement.
An isolated polynucleotide comprising a nucleotide sequence having at least 90% identity to SEQ ID NO:2 or SEQ ID NO:4.
Dependencies are inferred from the claim text.