Samholides, Swinholide-Related Metabolites from a Marine Cyanobacterium cf. <i>Phormidium</i> sp.

Cancer cell cytotoxicity was used to guide the isolation of nine new swinholide-related compounds, named samholides A–I (<b>1</b>–<b>9</b>), from an American Samoan marine cyanobacterium cf. <i>Phormidium</i> sp. Their structures were determined by extensive analysis of 1D and 2D NMR spectroscopic data. The new compounds share an unusual 20-demethyl 44-membered lactone ring composed of two monomers, and they demonstrate structural diversity arising from geometric isomerization of double bonds, sugar units with unique glyceryl moieties and varied methylation patterns. All of the new samholides were potently active against the H-460 human lung cancer cell line with IC₅₀ values ranging from 170 to 910 nM. The isolation of these new swinholide-related compounds from a marine cyanobacterium reinvigorates questions concerning the evolution and biosynthetic origin of these natural products

Biosynthetically Intriguing Chlorinated Lipophilic Metabolites from Geographically Distant Tropical Marine Cyanobacteria

Five new vinylchlorine-containing metabolites, the lipoamides janthielamide A and kimbeamides A–C and the ketide-extended pyranone kimbelactone A, have been isolated from collections of marine cyanobacteria made in Curaçao and Papua New Guinea. Both janthielamide A and kimbeamide A exhibited moderate sodium channel blocking activity in murine Neuro-2a cells. Consistent with this activity, janthielamide A was also found to antagonize veratridine-induced sodium influx in murine cerebrocortical neurons. These lipoamides represent the newest additions to a relatively rare family of marine cyanobacterial-derived lipoamides and a new structural class of compounds exhibiting neuromodulatory activities from marine cyanobacteria

JHB MS Data

Data from the LCMS chromatography of M. producens JHB and pure compound MS2 spectra from direct injection; in both .RAW and .mzXML format compressed in a .zip archive

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. <i>Trichodesmium</i> sp. nov.

Credneramides A (<b>1</b>) and B (<b>2</b>), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. <i>Trichodesmium</i> sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (<b>3</b>), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (<b>1</b>, IC₅₀ 4.0 μM; <b>2</b>, IC₅₀ 3.8 μM)

TOCSY and key HMBC correlations in hectoramide (4).

<p>TOCSY and key HMBC correlations in hectoramide (4).</p

Hectochlorin (1) isotope pattern within the <i>M</i>. <i>producens</i> JHB network.

<p>The presence of ³⁵Cl or ³⁷Cl within specific hectochlorin molecules yielded different parent masses and fragment spectra. The species with both ³⁵Cl atoms has an <i>m/z</i> of 665, the species with one ³⁵Cl and one ³⁷Cl atom has and <i>m/z</i> of 667, and the species with ³⁷Cl atoms has an <i>m/z</i> of 669. Because of this the fragment spectra share only masses from those fragments without chlorine atoms, and those fragments bearing the chlorine atoms show the same mass differences as their parent masses.</p

Visualization of MS data with Molecular Networking.

<p>The process of forming a molecular network begins with collection of MS¹ spectra (Step 1), from which parent ions are selected for MS² fragmentation (Step 2). After the data is acquired it is processed by the Spectral Networking algorithm which converts MS² data to vectors. The minimum number of peaks required to construct a vector is six; in this figure it is represented as only three so that the vector could be presented visually. It is important to note that when the multi-dimensional vectors are compared against all others by cosine function the vectors can have hundreds of dimensions (Step 3). This output is then visualized in Cytoscape with each node representing a MS² spectrum labeled and colored based on its parent mass (Step 4).</p

The Expanded Metabolome of <i>Moorea producens</i> JHB Described in this Study.

<p>The carbon atoms are numbered as they are in the text and supporting information.</p

The jamaicamide cluster of nodes within the Molecular Network of <i>Moorea producens</i> JHB.

<p>As with the hectochlorins, shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133297#pone.0133297.g003" target="_blank">Fig 3</a>, the jamaicamides are present in the network as multiple parent masses from the presence of heavy halogen atoms.</p

Expanding the Described Metabolome of the Marine Cyanobacterium <i>Moorea producens</i> JHB through Orthogonal Natural Products Workflows

<div><p><i>Moorea producens</i> JHB, a Jamaican strain of tropical filamentous marine cyanobacteria, has been extensively studied by traditional natural products techniques. These previous bioassay and structure guided isolations led to the discovery of two exciting classes of natural products, hectochlorin (<b>1</b>) and jamaicamides A (<b>2</b>) and B (<b>3</b>). In the current study, mass spectrometry-based ‘molecular networking’ was used to visualize the metabolome of <i>Moorea producens</i> JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes. Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and hectochlorin families. Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class. This study demonstrated that these orthogonal approaches are complementary and enrich secondary metabolomic coverage even in an extensively studied bacterial strain.</p></div