Biosynthetic gene cluster for the production of peptide/protein analogues
AssigneeETH Zurich
InventorsJorn Piel, Cristian Gurgui, Michael Francis Freeman, Agustinus Robert Uria, Maximilian Johannes Helf
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Abstract
A novel gene cluster encoding polypeptides involved in the generation of bio synthetically unique peptide-based compounds is described. In addition, new methods for biosynthetic engineering and production of modified peptides and proteins are disclosed. Furthermore, new tools for identification of homologue polypeptides and precursor peptides in other species are provided. In addition, peptide-based compounds and fusions of these compounds with functional moieties for treatment of disorders such as tumors are disclosed.
Claims18
A nucleic acid molecule or a composition of nucleic acid molecules comprising:
- (a) a nucleotide sequence of SEQ ID NO:
- 1;
- (b) a nucleotide sequence capable of hybridizing to the nucleotide sequence of SEQ ID NO:
- 1 under stringent hybridization conditions and encoding at least one polypeptide which catalyzes at least one step of the biosynthesis of polytheonamides and/or encoding a precursor peptide thereof;
- (c) a nucleotide sequence encoding at least one polypeptide or peptide selected from any one of poyA (SEQ ID NO:
- 3), poyB (SEQ ID NO:
- 5), poyC (SEQ ID NO:
- 7), poyD (SEQ ID NO:
- 9), poyE (SEQ ID NO:
- 11), poyF (SEQ ID NO:
- 13), poyG (SEQ ID NO:
- 15), poyH (SEQ ID NO:
- 17), poyI (SEQ ID NO:
- 19), poyK (SEQ ID NO:
- 21) and/or poyJ (SEQ ID NO:
- 23);
- (d) a nucleotide sequence encoding at least one polypeptide which catalyzes at least one step of the biosynthesis of polytheonamides and/or encoding a precursor peptide thereof which amino acid sequence is modified compared to the amino acid sequence of any one of poyA (SEQ ID NO:
- 3), poyB (SEQ ID NO:
- 5), poyC (SEQ ID NO:
- 7), poyD (SEQ ID NO:
- 9), poyE (SEQ ID NO:
- 11), poyF (SEQ ID NO:
- 13), poyG (SEQ ID NO:
- 15), poyH (SEQ ID NO:
- 17), poyI (SEQ ID NO:
- 19), poyK (SEQ ID NO:
- 21) and/or poyJ (SEQ ID NO:
- 23) by way of one or more amino acid substitution(s), deletion(s) and/or insertion(s);
- (e) a variant or portion of a nucleotide sequence of any one of (a) to (d) encoding at least one polypeptide which catalyzes at least one step of the biosynthesis of polytheonamides and/or encoding a precursor peptide thereof;
- (f) a nucleotide sequence which is degenerated with respected to the nucleotide sequence of any one of (a) to (e);
- or
- (g) a nucleotide sequence which is complementary to the nucleotide sequence in any one of (a) to (f).
(canceled)
Dependencies are inferred from the claim text.