Method for modifying microcystins and nodularins

21:

• The method according to claim 20, wherein the cyanobacteria strain is selected such that the incorporation of the one or more modified substrates into the non-ribosomal peptide occurs at a defined position.

22:

• The method according to claim 20, wherein the non-ribosomal peptide is a microcystin of the following general structure:
• D-Ala1-X2-D-MeAsp3-Z4-Adda5-DGlu6-Mdha7
• and wherein the one or more modified substrates are incorporated in at least one position other than Adda5 and DGlu6.

23:

• The method according to claim 22, wherein the incorporation of said one or more modified substrates occurs in position X2 and/or Z4.

24:

• The method according to claim 20, wherein the non-ribosomal peptide is a nodularin of the following general structure:
• D-MeAsp1-Arg2-Adda3-DGlu4-Mdhb5
• and wherein the one or more modified substrates are incorporated at any position other than Adda3 and DGlu4.

25:

• The method according to claim 24, wherein the incorporation of said one or more modified substrates occurs in position Arg2.

26:

• The method according to claim 22, wherein the modified position is X2 and the one or more modified substrates are a modified amino acid.

27:

• The method according to claim 22, wherein the modified position is Z4 and the one or more modified substrates are a modified amino acid.

28:

• The method according to claim 24, wherein the modified position is Arg2 and the one or more modified substrates are a modified amino acid.

29:

• The method according to claim 20, wherein the one or more modified substrate is at least one substrate selected from the group consisting of (2S)-2-amino-3-azidopropanoic acid, (2S)-2-amino-6-azidohexanoic acid, (S)-2-Amino-5-azidopentanoic acid, (2S)-2-amino-3-(4-prop-2-ynyloxyphenyl)propanoic acid, (2S)-2-amino-5-(N′-nitrocarbamimidamido)pentanoic acid, (2S)-2-amino-3-(furan-2-yl)propanoic acid, (S)-Amino-6-((prop-2-ynyloxy)carbonylamino)hexanoic acid, N-Propargyl-Lysine, (2S)-2-Amino-3-(4-azidophenyl)propanoic acid, and L-α-Amino-ε-guanidinohexanoic acid.

32:

• The method according to claim 20, wherein the concentration of the one or more modified substrates in the culture medium is between 5 μM and 500 μM and/or DMSO is added as an additional ingredient.

33:

• The method according to claim 20, wherein the conjugation chemistry is at least one selected from the group consisting of copper(I)-catalyzed azide-alkyne cycloaddition, strain promoted azide-alkyne cycloaddition, alkyne-azide cycloaddition, alkene-tetrazine inverse-demand Diels-Alder reaction, and reactions exploiting the specific reactivities of primary amines, thiols, aldehydes, carboxyls, and oximes.

34:

• The method according to claim 20, wherein the cyanobacteria strain is at least one selected from the group consisting of Microcystis, Planktothrix, Oscillatoria, Nostoc, Anabaena, Aphanizomenon, Hapalosiphon, Nodularia, Lyngbya, Phormidium, Spirulina, Halospirulina, Arthrospira, Trichodesmium, Leptolyngbya, Plectonema, Myxosarcina, Pleurocapsa, Pseudanabaena, Geitlerinema, Euhalothece, Calothrix, Tolypothrix, Scytonema, Fischerella, Mastigocladus, Westiellopsis, Stigonema, Chlorogloeopsis, Cyanospira, Cylindrospermopsis, Cylindrospermum, Microchaete, Rivularia, Autosira, Trichonema, Trichodesmium, Symploca, Starria, Prochlorothrix, Microcoleus, Limnothrix, Crinalium, Borzia, Chroococcidiopsis, Cyanocystis, Dermocarpella, Staniera, Xenococcus, Chamaesiphon, Chroococcus, Cyanobacterium, Cyanobium, Cyanothece, Dactylococcopsis, Gloeobacter, Gloeocapsa, and Gloeothece.

35:

• A method of producing a compound for targeted therapy comprising a non-ribosomal peptide linked to a targeting moiety, the method comprising:
• A) providing a targeting moiety and a non-ribosomal peptide comprising at least one modified amino acid, wherein the at least one modified amino acid comprises an anchor group directly accessible or transformable for use in conjugation chemistry by performing a method according to claim 20, and
• B) attaching said targeting moiety to said non-ribosomal peptide via chemical conjugation to said anchor group.

36:

• The method according to claim 35, wherein the targeting moiety is attached via a linker arranged between the modified amino acid and the targeting moiety.

37:

• The method according to claim 35, wherein the targeting moiety is an antibody.

38:

• The method according to claim 20, wherein the one or more modified substrates are the modified amino acid which comprises an anchor group directly accessible or transformable for use in click chemistry.