VARIANT LovD POLYPEPTIDE
AssigneeThe Regents of the University of California
InventorsYi Tang, Xue Gao, Xinkai Xie
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Abstract
The invention disclosed herein relates to methods and materials for producing simvastatin and related compounds such as huvastatin. In particular, the disclosure teaches that variants of the LovD acyltransferase polypeptide can be engineered to exhibit properties that facilitate their use in the production of simvastatin and/or huvastatin. The materials and processes disclosed herein are designed so that fermentation facilities lovastatin being converted to simvastatin and related compounds with minimal modifications.
Claims20
A method of making a variant of a LovD polypeptide shown in SEQ ID NO:1 comprising:
- using a polynucleotide mutagenesis procedure to generate a population of mutants of the LovD polynucleotide shown in SEQ ID NO:
- 5, wherein the population of mutant LovD polynucleotides encodes LovD polypeptide variants having at least one amino acid substitution selected from the group consisting of K26E, G275S, or L361M;
- and
- expressing a population of LovD polypeptide variants encoded by the population of LovD polynucleotide mutants;
- so that a variant of a LovD polypeptide shown in SEQ ID NO:1 is made.
A polynucleotide encoding a variant LovD polypeptide, wherein:
- the variant LovD polypeptide comprises a functional LovD acyltransferase with an amino acid sequence having at least 90% identity to SEQ ID NO:1;
- and
- the variant LovD polypeptide comprises an amino acid substitution at amino acid residue position selected from the group consisting of:
- A10;
- D12;
- K26;
- A86;
- A190;
- H161;
- K227;
- G275;
- V334;
- and L361 of SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.