Abstract: The present invention relates to the application of biosynthetic engineering for the heterologous expression of a gene cluster for the biosynthesis of tetracycline compounds, notably chelocardin and its analogues. More particularly, the present invention pertains to a gene cluster encoding polypeptides involved in tetracycline biosynthesis, which gene cluster is suitable for heterologous expression of the biosynthetic pathway in a host cell. The present invention further pertains to DNA construct s comprising the gene cluster, to recombinant heterologous host cell s comprising the gene cluster or the DNA construct, to processes for the biosynthetic production of a tetracycline compound employing such recombinant host cells, and to tetracycline compounds thereby produced. The present invention also pertains to fusion proteins which are useful in the production of tetracycline compounds.

Abstract: This invention relates to an engineered leader-independent heterocyclase (also known as a cyclodehydratase) comprising a defined cyanobactin leader sequence which drives the efficient conversion of heterocyclisable amino acids, such as Ser, Thr and Cys, within a peptide substrate lacking a leader sequence into heterocycles produce a homogenous heterocycle-containing product. This may be useful in biotechnology and chemical synthesis.

Abstract: This invention relates to the in vitro production of cyclic peptides using cyanobacterial enzymes, such as patellamide biosynthesis enzymes. Linear peptide substrates are cyclized using an isolated cyanbacterial macrocyclase, such as PatG from Prochloron spp. Before cyclization, residues in the linear peptide substrates may be heterocyclized using isolated cyanbacterial heterocyclasses, such as PatD or TruD heterocyclase. Methods of the invention may be useful, for example, for the production of cyclic peptidyl molecules, including cyclotides, such as katalas, and cyanobactins, such as patellamides and telomestatins, for example for use in the development of therapeutics.

Abstract: This invention relates to an engineered leader-independent heterocyclase (also known as a cyclodehydratase) comprising a defined cyanobactin leader sequence which drives the efficient conversion of heterocyclisable amino acids, such as Ser, Thr and Cys, within a peptide substrate lacking a leader sequence into heterocycles produce a homogenous heterocycle-containing product. This may be useful in biotechnology and chemical synthesis.

Abstract: This invention relates to the in vitro production of cyclic peptides using cyanobacterial enzymes, such as patellamide biosynthesis enzymes. Linear peptide substrates are cyclized using an isolated cyanbacterial macrocyclase, such as PatG from Prochloron spp. Before cyclisation, residues in the linear peptide substrates may be heterocyclised using isolated cyanbacterial heterocyclasses, such as PatD or TruD heterocyclase. Methods of the invention may be useful, for example, for the production of cyclic peptidyl molecules, including cyclotides, such as katalas, and cyanobactins, such as patellamides and telomestatins, for example for use in the development of therapeutics.

Abstract: This invention relates to the in vitro production of cyclic peptides using cyanobacterial enzymes, such as patellamide biosynthesis enzymes. Linear peptide substrates are cyclized using an isolated cyanbacterial macrocyclase, such as PatG from Prochloron spp. Before cyclisation, residues in the linear peptide substrates may be heterocyclised using isolated cyanbacterial heterocyclases, such as PatD or TruD heterocyclase. Methods of the invention may be useful, for example, for the production of cyclic peptidyl molecules, including cyclotides, such as katalas, and cyanobactins, such as patellamides and telomestatins, for example for use in the development of therapeutics.

Abstract: The present invention relates to a method for determining SUMOylation and utilizing said SUMOylation patterns for identifying specific interaction between different binding partners. In another aspect, the present invention relates to systems allowing the determination of SUMOylation and for determining specific interaction between binding partners. Furthermore, the present invention relates to vectors and proteins relating to SUMOylation.

Abstract: The present invention relates to a method for determining SUMOylation and utilizing said SUMOylation patterns for identifying specific interaction between different binding partners. In another aspect, the present invention relates to systems allowing the determination of SUMOylation and for determining specific interaction between binding partners. Furthermore, the present invention relates to vectors and proteins relating to SUMOylation.

Abstract: The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein, which peptides are lethal to malignant or transformed cells when fused to a membrane-penetrating leader sequence. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide fused at its carboxy terminal end to a membrane penetrating leader sequence are also provided. The present invention also provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence operably linked to a nucleotide sequence encoding a subject peptide. Methods of selectively killing cancer cells in a subject by administering a therapeutically effective amount of a subject AdV vector are also provided by the present invention.

Abstract: The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein, which peptides are lethal to malignant or transformed cells when fused to a membrane-penetrating leader sequence. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide fused at its carboxy terminal end to a membrane penetrating leader sequence are also provided. The present invention also provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence operably linked to a nucleotide sequence encoding a subject peptide. Methods of selectively killing cancer cells in a subject by administering a therapeutically effective amount of a subject AdV vector are also provided by the present invention.