Resolution of the Confusion in the Assignments of Configuration for the Ciliatamides, Acylated Dipeptides from Marine Sponges

Direct comparison of authentic ciliatamide A with four synthetic isomers (<b>1</b>–<b>4</b>) by means of NMR and chiral-phase HPLC revealed that ciliatamide A possesses the 12<i>R</i> (d-<i>N</i>-MePhe residue) and 22<i>S</i> (l-Lys residue) configurations, which were not identical with either our previous assignment or those proposed by others through total synthesis. The absolute configuration of the methionine sulfoxide residue in ciliatamide D was also revised to be d

First Detection of Tetrodotoxins in the Cotylean Flatworm Prosthiostomum trilineatum

Several polyclad flatworm species are known to contain high levels of tetrodotoxin (TTX), but currently TTX-bearing flatworms seem to be restricted to specific Planocera lineages belonging to the suborder Acotylea. During our ongoing study of flatworm toxins, high concentrations of TTXs were detected for the first time in the flatworm Prosthiostomum trilineatum, suborder Cotylea, from the coastal area of Hayama, Kanagawa, Japan. Toxin levels were investigated by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), revealing that this species contains comparable concentrations of toxins as seen in planocerid flatworms such as Planocera multitentaculata. This finding indicated that there may be other species with significant levels of TTXs. The distribution of TTXs among other flatworm species is thus of great interest

Characterization and phylogenetic position of two sympatric sister species of toxic flatworms Planocera multitentaculata and Planocera reticulata (Platyhelminthes: Acotylea)

The complete mitochondrial genomes of two toxic flatworm species of the genus Planocera were determined. The total length of mitochondrial DNA (mtDNA) was 15,657 bp in Planocera multitentaculata and 15,486 bp in Planocera reticulata and included 12 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 4 non-coding regions. The mitochondrial gene arrangement of these planocerid species was identical to that of previously described acotylean species, Hoploplana elisabelloi, and also to those of other polyclads. Maximum likelihood analysis against 14 Platyhelminthes showed that a tree was robustly constructed using 12 protein-coding genes than COI gene

Miuramides A and B, Trisoxazole Macrolides from a <i>Mycale</i> sp. Marine Sponge That Induce a Protrusion Phenotype in Cultured Mammalian Cells

Morphology-guided cell-based screening of the extract of a <i>Mycale</i> sp. marine sponge led to the isolation of two trisoxazole macrolides, miuramides A (<b>1</b>) and B (<b>2</b>), which induced characteristic morphological changes in 3Y1 cells. The structure of <b>1</b> including absolute configuration was elucidated by a combination of the analysis of spectroscopic data, derivatization, and degradation. Both compounds exhibit potent cytotoxicity against 3Y1 cells

Phylogenetic position of the Atlantic Gnomefish, Scombrops oculatus (Teleostei: Scombropidae), within the genus Scombrops, inferred from the sequences of complete mitochondrial genome and cytochrome c oxidase subunit I genes

We determined the complete mitochondrial genome of the Atlantic Gnomefish, Scombrops oculatus (Scombropidae). The total length of mitochondrial DNA (mtDNA) was 16,515 bp and included 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene arrangement of S. oculatus was identical to those of three Japanese scombropid species and those of other teleosts. The phylogenetic analysis using the whole mtDNA, excluding the control region, indicates the Atlantic species is distinct from the Japanese clade, whereas that using cytochrome c oxidase subunit I gene showed the Atlantic species is most closely related to the African species

Local Differences in the Toxin Amount and Composition of Tetrodotoxin and Related Compounds in Pufferfish (Chelonodon patoca) and Toxic Goby (Yongeichthys criniger) Juveniles

Tetrodotoxin (TTX)-bearing fish ingest TTX from their preys through the food chain and accumulate TTX in their bodies. Although a wide variety of TTX-bearing organisms have been reported, the missing link in the TTX supply chain has not been elucidated completely. Here, we investigated the composition of TTX and 5,6,11-trideoxyTTX in juveniles of the pufferfish, Chelonodon patoca, and toxic goby, Yongeichthys criniger, using LC&ndash;MS/MS, to resolve the missing link in the TTX supply chain. The TTX concentration varied among samples from different localities, sampling periods and fish species. In the samples from the same locality, the TTX concentration was significantly higher in the toxic goby juveniles than in the pufferfish juveniles. The concentration of TTX in all the pufferfish juveniles was significantly higher than that of 5,6,11-trideoxyTTX, whereas the compositional ratio of TTX and 5,6,11-trideoxyTTX in the goby was different among sampling localities. However, the TTX/5,6,11-trideoxyTTX ratio in the goby was not different among samples collected from the same locality at different periods. Based on a species-specific PCR, the detection rate of the toxic flatworm (Planocera multitentaculata)-specific sequence (cytochrome c oxidase subunit I) also varied between the intestinal contents of the pufferfish and toxic goby collected at different localities and periods. These results suggest that although the larvae of the toxic flatworm are likely to be responsible for the toxification of the pufferfish and toxic goby juveniles by TTX, these fish juveniles are also likely to feed on other TTX-bearing organisms depending on their habitat, and they also possess different accumulation mechanisms of TTX and 5,6,11-trideoxyTTX

Poecillastrin H, a Chondropsin-Type Macrolide with a Conjugated Pentaene Moiety, from a <i>Characella</i> sp. Marine Sponge

Poecillastrin H (<b>1</b>), a chondropsin-type macrolide with a conjugated pentaene moiety, was isolated from the <i>Characella</i> sp. marine sponge. The planar structure of <b>1</b> was elucidated by analysis of spectroscopic data. The absolute configuration of the β-hydroxyaspartic acid residue (β-OHAsp) was determined to be d-<i>threo</i> by Marfey’s analysis, and the mode of lactone ring formation through the OHAsp residue was determined by chemical degradation. Poecillastrin H was extremely sensitive toward light and showed potent cytotoxic activity against 3Y1 cells with an IC₅₀ value of 4.1 nM

Levels of Tetrodotoxins in Spawning Pufferfish, <i>Takifugu alboplumbeus</i>

Tetrodotoxin (TTX), also known as pufferfish toxin, is an extremely potent neurotoxin thought to be used as a biological defense compound in organisms bearing it. Although TTX was thought to function as a chemical agent for defense and anti-predation and an attractant for TTX-bearing animals including pufferfish, it has recently been demonstrated that pufferfish were also attracted to 5,6,11-trideoxyTTX, a related compound, rather than TTX alone. In this study, we attempted to estimate the roles of TTXs (TTX and 5,6,11-trideoxyTTX) in the pufferfish, Takifugu alboplumbeus, through examining the location of TTXs in various tissues of spawning pufferfish from Enoshima and Kamogawa, Japan. TTXs levels in the Kamogawa population were higher than those in the Enoshima population, and there was no significant difference in the amount of TTXs between the sexes in either population. Individual differences were greater in females than in males. However, the location of both substances in tissues differed significantly between sexes: male pufferfish accumulated most of their TTX in the skin and liver and most of their 5,6,11-trideoxyTTX in the skin, whereas females accumulated most of their TTX and 5,6,11-trideoxyTTX in the ovaries and skin

Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium

Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters, suggesting a rich and mostly uncharacterized specialized metabolism. Here, in silico chemical prediction of a non-canonical polyketide synthase cluster has led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of C-13 chemical shifts and semiquantitative interpretation of transverse rotating-frame Overhauser effect spectroscopy data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment of the absolute configuration. Janustatins feature a previously unknown pyridodihydropyranone heterocycle and an unusual biological activity consisting of delayed, synchronized cell death at subnanomolar concentrations.ISSN:1755-4349ISSN:1755-433