Anabaenopeptins from Nostoc edaphicum CCNP1411

Abstract

Cyanobacteria of the Nostoc genus belong to the most prolific sources of bioactive metabolites. In our previous study on Nostoc edaphicum strain CCNP1411, the occurrence of cyanopeptolins and nostocyclopeptides was documented. In the current work, the production of anabaenopeptins (APs) by the strain was studied using genetic and chemical methods. Compatibility between the analysis of the apt gene cluster and the structure of the identified APs was found. Three of the APs, including two new variants, were isolated as pure compounds and tested against four serine proteases and carboxypeptidase A (CPA). The in vitro enzymatic assays showed a typical activity of this class of cyanopeptides, i.e., the most pronounced effects were observed in the case of CPA. The activity of the detected compounds against important metabolic enzymes confirms the pharmaceutical potential of anabaenopeptins.

Structural Diversity and Biological Activity of Cyanopeptolins Produced by Nostoc edaphicum CCNP1411

“…In CCNP1411, three classes of non-ribosomal peptides were identified. This includes: anabaenopeptins with four structural variants [98], nostocyclopeptides with six linear and five cyclic variants [99], and thirteen cyanopeptolins [8]. In the current study, the number of CPs variants detected in CCNP1411 increased to 93.…”

“…The enzyme inhibitory activity of cyanopeptolins was assayed against trypsin [108], chymotrypsin, thrombin [109], and elastase [57] as described before [98]. In brief, the samples were prepared and serially diluted (1 mg, 1:1-1:10,000 times) in 1% DMSO; the standard inhibitors: aprotinin (trypsin and chymotrypsin) AEBSF 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (thrombin), elastatinal (elastase) (all from Sigma Aldrich; St. Louis, MO, USA) were also prepared in 1% DMSO.…”

Natural Products That Contain Higher Homologated Amino Acids

“…The backbone structure of RiPPs is synthesized by the ribosome, and each residue is modified by tailoring enzymes [117] . All homoAA‐containing NPs whose biosynthesis is known or proposed are NRPs [16b,17a,18a,c,d,24d,25a,28c,30,43b,51a,56–57,58c,59,63–64,65c,70,72,84l,91a,c,93c,118] with a few exceptions, including phaseolotoxin (Figure 14), [119] ophthalmic acid (Figure 20), [112] and fungal compounds 7 and 8 (Figure 17). [98] As many of the proposed or characterized homologation pathways require the modification of the backbone structure, it would be more reasonable that the NRP structure is assembled after homologation happens to the amino acid.…”

“…In the biosynthesis of the cyanobacterial NPs anabaenopeptins that contain hPhe and/or hTyr, the genes encoding homologous enzymes of IPMS, IPMI, IPMD, and/or ArAT are found in the BGC of the parent NRP [16b,17a,18a,d,30,118f] . ArAT may be absent likely because ArAT that is a part of primary metabolic pathways and present outside of the BGC is also utilized for the production of hPhe and hTyr.…”