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

Abstract

Nostocyclopeptides (Ncps) constitute a small class of nonribosomal peptides, exclusively produced by cyanobacteria of the genus Nostoc. The peptides inhibit the organic anion transporters, OATP1B3 and OATP1B1, and prevent the transport of the toxic microcystins and nodularin into hepatocytes. So far, only three structural analogues, Ncp-A1, Ncp-A2 and Ncp-M1, and their linear forms were identified in Nostoc strains as naturally produced cyanometabolites. In the current work, the whole genome sequence of the new Ncps producer, N. edaphicum CCNP1411 from the Baltic Sea, has been determined. The genome consists of the circular chromosome (7,733,505 bps) and five 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 and characterized in silico. The LC-MS/MS analyzes of N. edaphicum CCNP1411 cell extracts prepared in aqueous methanol revealed several products of the genes. Besides the known peptides, Ncp-A1 and Ncp-A2, six other compounds putatively characterized as new noctocyclopeptide analogues were detected. This includes Ncp-E1 and E2 and their linear forms (Ncp-E1-L and E2-L), a cyclic Ncp-E3 and a linear Ncp-E4-L. Regardless of the extraction conditions, the cell contents of the linear nostocyclopeptides were found to be higher than the cyclic ones, suggesting a slow rate of the macrocyclization process.

Nostocyclopeptides as New Inhibitors of 20S Proteasome

“…Thus far, the presence of Ncps was reported in five strains of Nostoc isolated from different habitats [20,23,[29][30][31]. This includes two Baltic strains: XSPORK 13A producing the cyclic Ncp-M1 [23] and CCNP1411 producing 10 other Ncps variants [31].…”

“…Thus far, the presence of Ncps was reported in five strains of Nostoc isolated from different habitats [20,23,[29][30][31]. This includes two Baltic strains: XSPORK 13A producing the cyclic Ncp-M1 [23] and CCNP1411 producing 10 other Ncps variants [31]. The putative structures of the five linear and five cyclic Ncps variants produced by CCNP1411 were elucidated based on mass spectra fragmentation patterns [31].…”

“…This includes two Baltic strains: XSPORK 13A producing the cyclic Ncp-M1 [23] and CCNP1411 producing 10 other Ncps variants [31]. The putative structures of the five linear and five cyclic Ncps variants produced by CCNP1411 were elucidated based on mass spectra fragmentation patterns [31]. Two of the cyclic forms, Ncp-A1 and Ncp-A2, enclosed by imino linkage between the N-terminal amine group of conserved Tyr and C-terminal aldehyde group of Leu or Phe, were previously identified in Nostoc sp.…”

Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

“…Other examples of cyanobacterial molecules produced by hybrid systems are barbamides [ 267 ] ( Figure 11 ), nostopeptolides [ 268 ], microginins, which exhibit multiple clinically interesting bioactivities [ 269 , 270 ], laxaphicins, with synergistic cytotoxic and antifungal activity [ 271 , 272 ], or the recently characterized cryptomaldamides ( Figure 11 ), discovered through matrix-assisted laser desorption/ionization (MALDI) analyses of individual filaments of Moorea producens fed with heavy nitrogen and whose BGC was later cloned and heterologously expressed in Anabaena PCC7120 for further characterization [ 254 , 273 ]. On the other hand, molecules like aeruginosins, anabaenopeptin ( Figure 11 ), nostocyclopeptides [ 274 , 275 ], the antifungal cyclic lipopeptide hassalidins [ 276 , 277 ] among others, are the product of NRPS-only clusters. Anatoxin-a ( Figure 11 ) and saxitoxin are potent alkaloid neurotoxins derived from PKS BGCs instead [ 278 , 279 ].…”

Algal Toxic Compounds and Their Aeroterrestrial, Airborne and other Extremophilic Producers with Attention to Soil and Plant Contamination: A Review

“…Ncps were firstly isolated in two variants (Ncp-A1 and Ncp-A2) from the Nostoc strain ATCC5389 from the Aaron Island (Scotland), reported earlier as a Cr-producer [ 144 , 165 ]. More recently, two new Ncps producers were purified from the Baltic Sea [ 117 , 167 ]: Nostoc , isolated from a gastropod symbiont, strain XSPORK 13A, which formed different Ncps variant Ncp-M1 (and later was found to form also seven variants of nostoweipeptins, W1-W7 [ 164 ]) [ 117 ] and a free-living N. edaphicum CCNP1411 [ 167 ]. The last one, besides the known peptides, Ncp-A1 and Ncp-A2, contained six other compounds (Ncp-E1-L and E2-L, Ncp-E3 and Ncp-E4-L) putatively defined as new Ncp analogues [ 167 ].…”