Nostoc edaphicum CCNP1411 from the Baltic Sea—A New Producer of Nostocyclopeptides

Abstract

Nostocyclopeptides (Ncps) constitute a small class of nonribosomal peptides, exclusivelyproduced by cyanobacteria of the genusNostoc. The peptides inhibit the organic anion transporters,OATP1B3 and OATP1B1, and prevent the transport of the toxic microcystins and nodularin intohepatocytes. So far, only three structural analogues, Ncp-A1, Ncp-A2 and Ncp-M1, and their linearforms were identified inNostocstrains as naturally produced cyanometabolites. In the current work,the whole genome sequence of the new Ncps producer,N.edaphicumCCNP1411 from the BalticSea, has been determined. The genome consists of the circular chromosome (7,733,505 bps) andfive circular plasmids (from 44.5 kb to 264.8 kb). The nostocyclopeptide biosynthetic gene cluster(located between positions 7,609,981–7,643,289 bps of the chromosome) has been identified andcharacterizedin silico. The LC-MS/MS analyzes ofN.edaphicumCCNP1411 cell extracts preparedin aqueous methanol revealed several products of the genes. Besides the known peptides, Ncp-A1and Ncp-A2, six other compounds putatively characterized as new noctocyclopeptide analogueswere detected. This includes Ncp-E1 and E2 and their linear forms (Ncp-E1-L and E2-L), a cyclicNcp-E3 and a linear Ncp-E4-L. Regardless of the extraction conditions, the cell contents of the linearnostocyclopeptides were found to be higher than the cyclic ones, suggesting a slow rate of themacrocyclization process.