Natural antifoulants from the marine cyanobacterium Lyngbya majuscula

Filamentous benthic marine cyanobacteria are a prolific source of structurally unique bioactive secondary metabolites. A total of 12 secondary metabolites, belonging to the mixed polyketide–polypeptide structural class, were isolated from the marine cyanobacterium, Lyngbya majuscula, and were tested to determine if they showed activity against barnacle larval settlement. The assays revealed four compounds, dolastatin 16 (1), hantupeptin C (4), majusculamide A (10), and isomalyngamide A (12), that showed moderate to potent anti-larval settlement activities, with EC₅₀ values ranging from 0.003 to 10.6 μg ml^?1. In addition, field testing conducted over a period of 28 days (using the modified Phytagel? method) based on the cyanobacterial compound, dolastatin 16, showed significantly reduced barnacle settlement as compared to controls at all the concentrations tested. The results of this study highlight the importance of marine cyanobacteria as an underexplored source of potential environmentally friendly antifoulants.     

Five new indole derivatives from the cyanobacterium Moorea producens

Chemical analysis of the hydrophilic fraction from marine cyanobacterium Moorea producens extracts led to the isolation of five new indole derivatives (1-5). So far, 2-formyl-4,5,6,7-tetrahydroindole has been reported only for 6 from the nature, consequently compounds 1-5 were the second representatives of this class. Cytotoxicity, diatom growth inhibition, and antibacterial activity tests for compounds 1-5 showed no bioactivity at the concentration tested.     

Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula

Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar, Singapore. The complete structural characterization of the molecule was achieved by extensive NMR spectroscopic analysis as well as chemical manipulations. Several methods, including the advanced Marfey’s method, a modified method based on derivatization with Mosher’s reagents and analysis using LC–MS, and the use of ³J_H–H coupling constant values, were utilized for the determination of its absolute configuration. Compound 1 is related to the aurilide-class of molecules and it differs mainly in the macrocyclic structure by having a 27 membered ring system due to additional methylene carbon in the polyketide moiety. Lagunamide C displayed potent cytotoxic activity against a panel of cancer cell lines, such as P388, A549, PC3, HCT8, and SK-OV3 cell lines, with IC₅₀ values ranging from 2.1 nM to 24.4 nM. Compound 1 also displayed significant antimalarial activity with IC₅₀ value of 0.29 μM when tested against Plasmodium falciparum. In addition, lagunamide C exhibited weak anti-swarming activity when tested at 100 ppm against the Gram-negative bacterial strain, Pseudomonas aeruginosa PA01.     

Besarhanamides A and B from the marine cyanobacterium Lyngbya majuscula

Besarhanamides A (1) and B (2) are fatty acid amides purified from the marine cyanobacterium, Lyngbya majuscula, collected from Pulau Hantu, Singapore. The structure determination of these secondary metabolites was carried out using extensive 2D NMR spectral data as well as chemical manipulations including the Marfey's method. In addition, besarhanamide A exhibited moderate toxicity with LD(50) at 13 microM in the brine shrimp toxicity bioassay.     

Pitipeptolides C-F, antimycobacterial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula from Guam

Pitipeptolides A (1) and B (2) are cyclic depsipeptides isolated from the marine cyanobacterium Lyngbya majuscula from Piti Bomb Holes, Guam. Additional analogues have now been isolated by revisiting larger collections of the same cyanobacterium. The four identified analogues, pitipeptolides C–F (3–6), are the tetrahydro analogue (3), an analogue with a lower degree of methylation (4) as well as two homologues (5 and 6) of pitipeptolide A. Their structures were elucidated using 2D NMR experiments, chiral HPLC analysis and comparison with pitipeptolide A. The identified analogues showed weaker cytotoxic activities compared to the two major parent compounds, pitipeptolides A (1) and B (2), against HT-29 colon adenocarcinoma and MCF7 breast cancer cells. On the other hand, pitipeptolide F (6) was the most potent pitipeptolide in a disc diffusion assay against Mycobacterium tuberculosis. The latter finding suggests that the structure of pitipeptolides could be optimized for selective antibacterial activity.     

Hantupeptins B and C,cytotoxic cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula

Hantupeptins B (2) and C (3) were isolated, along with the previously reported hantupeptin A (1), from the marine cyanobacterium, Lyngbya majuscula, collected from Pulau Hantu Besar, Singapore. Their structures were elucidated by interpretation of extensive 1D and 2D NMR spectroscopic data. Compounds 2 and 3 are cyclic depsipeptides consisting of five α-amino/hydroxy acid residues, including phenyllactic acid, proline, N-methyl-valine, valine, N-methyl-isoleucine, and a β-hydroxy acid unit with different degrees of unsaturation at the terminal end of each molecule. The absolute configurations of the common amino acids and phenyllactic acid were determined by the advanced Marfey’s and chiral HPLC analyses, respectively. The complete stereochemistry of 3-hydroxy-2-methyl-7-octynoic acid moiety in hantupeptin A was elucidated by a combination of homonuclear J-resolved 2D NMR experiments and by Mosher’s method. Hantupeptins B and C showed moderate in vitro cytotoxicity when tested against MOLT-4 (leukemic) and MCF-7 (breast cancer) cell lines.     

Two malyngamides from the caribbean cyanobacterium Lyngbya majuscula

Chemical examination of two collections of the Caribbean cyanobacterium, Lyngbya majuscula, led us to isolate several antimicrobial agents. The most active was elemental sulphur, followed by the previously reported fatty acid (−)-7(S)-methoxytetradec-4(E)-enoate, and then by two new amides of this fatty acid, malyngamide D and malyngamide D acetate. The new compounds possess vinyl chloride and α,β-unsaturated enone functional groups. The structures of the new compounds are based on spectroscopic evidence including several 2D NMR techniques at high field as well as chemical interconversion.     

Total structure and biological properties of laxaphycins A and B, cyclic lipopeptides from the marine cyanobacterium Lyngbya majuscula

The tropical marine cyanobacterium Lyngbyamajuscula produces a series of cytotoxic andantimicrobial cyclic peptides. The totalstructure of the two major components,laxaphycins A and B, was determined byinterpretation of physical data, principallyhigh field NMR, FAB MS and MS/MS, in combinationwith chemical derivatization and degradationschemes. Absolute stereochemistries of thenatural and exotic amino acids weredetermined. The two cyclic peptides exhibited anunusual biological synergism when tested forantifungal or cytotoxic effects.     

Total structure and biological properties of laxaphycins A and B,cyclic lipopeptides from the marine cyanobacterium Lyngbya majuscula

Summary The tropical marine cyanobacteriumLyngbya majuscula produces a series of cytotoxic and antimicrobial cyclic peptides. The total structure of the two major components, laxaphycins A and B, was determined by interpretation of physical data, principally high field NMR, FAB MS and MS/MS, in combination with chemical derivatization and degradation schemes. Absolute stereochemistries of the natural and ‘exotic’ amino acids were determined. The two cyclic peptides exhibited an unusual biological synergism when tested for antifungal or cytotoxic effects.     

Immunolocalization of the uptake hydrogenase in the marine cyanobacterium Lyngbya majuscula CCAP 1446/4 and two Nostoc strains

In N₂-fixing cyanobacteria, the reduction of N₂ to NH₃ is coupled with the production of molecular hydrogen, which is rapidly consumed by an uptake hydrogenase, an enzyme that is present in almost all diazotrophic cyanobacteria. The cellular and subcellular localization of the cyanobacterial uptake hydrogenase remains uncertain, and it is definitely strain dependent. Previous studies focused mainly on heterocystous cyanobacteria and used heterologous antisera. The present work represents the first effort to establish the subcellular localization of the uptake hydrogenase in a N₂-fixing filamentous nonheterocystous cyanobacterium, Lyngbya majuscula CCAP 1446/4, using the first antiserum produced against a cyanobacterial uptake hydrogenase. The data obtained revealed higher specific labelling associated with the thylakoid membranes of L. majuscula , reinforcing the idea that the cyanobacterial uptake hydrogenase is indeed a membrane-bound protein. For comparative purposes, the localization of the uptake hydrogenase was also investigated in two distinct heterocystous cyanobacterial strains, and while in Nostoc sp. PCC 7120 the labelling was only observed in the heterocysts, in Nostoc punctiforme , the presence of uptake hydrogenase antigens was detected in both the vegetative cells and heterocysts, corresponding most probably to an inactive and an active form of the enzyme.     

Wewakamide A and guineamide G, cyclic depsipeptides from the marine cyanobacteria Lyngbya semiplena and Lyngbya majuscula

Two new cyclic depsipeptides wewakamide A (1) and guineamide G (2) have been isolated from the marine cyanobacterium Lyngbya semiplena and Lyngbya majuscula, respectively, collected from Papua New Guinea. The amino and hydroxy acid partial structures of wewakamide A and guineamide G were elucidated through extensive spectroscopic techniques, including HR-FABMS, 1D (1)H and (13)C NMR, as well as 2D COSY, HSQC, HSQCTOCSY, and HMBC spectra. The sequence of the residues of wewakamide A was determined through a combination of ESI-MS/MS, HMBC, and ROESY. Wewakamide A possesses a β-amino acid, 3-amino-2-methylbutanoic acid (Maba) residue, which has only been previously identified in two natural products, guineamide B (3) and dolastatin D (4). Although both new compounds (1,2) showed potent brine shrimp toxicity, only guineamide G displayed significant cytotoxicity to a mouse neuroblastoma cell line with LC(50) values of 2.7 micrometer.     

Pilot scale culture of the marine cyanobacterium Lyngbya majuscula for its pharmaceutically-useful natural metabolite curacin A

A Caribbean collection of Lyngbya majuscula which produces the promising antimitotic agent, curacin A, was recollected in 1993 from Curaçao and adapted to laboratory culture. A variety of culture vessel configurations and conditions were examined for their effect on growth and production of curacin A. Using these partially optimized conditions, 29 strains of curacin A producing L. majuscula were evaluated for their production levels of curacin A employing an internal standard GC-MS analytical method. Five strains were more carefully characterized for their growth and curacin A production, and led to our selection of one reliable strain, ’19L‘, for further studies. Growth and curacin A production curves were established for this strain over a 30 day growth period. This directed a scale-up culture of 640 liters of L. majuscula strain 19L in four batches of 160 L each. All four batches grew well and produced significant quantities of curacin A. In tota1, 215.5 g wet weight of L. majuscula tissue were produced which gave an isolated yield of 132.5 mg of curacin A.     

Culture of the marine cyanobacterium, Lyngbya majuscula (Oscillatoriaceae), for bioprocess intensified production of cyclic and linear lipopeptides.

Cyanobacteria are an ancient and diverse group of photosynthetic microorganisms, which inhabit many different and extreme environments. This indicates a high degree of biological adaptation, which has enabled these organisms to thrive and compete effectively in nature. The filamentous cyanobacterium, Lyngbya majuscula, produces several promising antifungal and cytotoxic agents, including laxaphycin A and B and curacin A. Samples of L. majuscula collected from Moorea Island, Tahiti (French Polynesia) and from the Culture Collection of Algae and Protozoa (CCAP 1446/4) were studied and adapted to large scale laboratory culture (5 l). This constitutes a 100-fold scale-up for the culture of this particular strain of L. majuscula. The effect of culture vessel configurations, growth conditions and media compositions on growth of L. majuscula was examined. Using optimised culture conditions, two strains of L. majuscula are currently being evaluated for their production of secondary metabolites. Results will be compared with those obtained from four environmental extracts. Comparisons were made by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). It was shown that varying the culture conditions under which L. majuscula was grown had the greatest effect on secondary metabolite production, thus providing potential for future bioprocess intensified production.     

Two cytotoxic stereoisomers of malyngamide C, 8-epi-malyngamide C and 8-O-acetyl-8-epi-malyngamide C,from the marine cyanobacterium Lyngbya majuscula

Two epimers of malyngamide C, 8-O-acetyl-8-epi-malyngamide C (1) and 8-epi-malyngamide C (3) have been isolated along with known compounds 6-O-acetylmalyngamide F (5), H (6), J (7) K (8), and characterized from a Grenada field collection of the marine cyanobacterium Lyngbya majuscula. The structures of these compounds were deduced by 1D and 2D NMR spectroscopic and mass spectral data interpretation. Absolute configurations were determined by a combination of CD-spectroscopy, chemical degradation and the variable temperature Mosher’s method. Compounds 1–5, 7 and 8 displayed moderate cytotoxicity to NCI-H460 human lung tumor and neuro-2a cancer cell lines, with IC₅₀ values ranging between 0.5 and 20 μg/mL.     

(+)-α(S)-butyramido-γ-butyrolactone from Lyngbya majuscula

(+)-α(S)-Butyramido-γ-butyrolactone is a minor constituent of the toxic marine blue-green alga Lyngbya majuscula.     

7-methoxy-9-methylhexadeca-4(E),8(E)-dienoic acid from Lyngbya majuscula

A new fatty acid, 7-methoxy-9-methylhexadeca- 4(E),8(E)-dienoic acid, has been isolated from a toxic, deep-water variety of the marine blue-green alga Lyngbya majuscula.     

A new ophichthid species from the Red Sea of the genus Mixomyrophis,formerly known as Atlantic genus

Ichthyological Research - A new species of worm eel (family Ophichthidae: subfamily Myrophinae), Mixomyrophis longidorsalis sp. nov. is described based on a single specimen [77.0 mm in total length...     

Evoxymetopon moricheni,a new cutlassfish from the northern Red Sea (Teleostei: Trichiuridae)

Evoxymetopon moricheni n. sp. is described from the northern Gulf of Aqaba, Red Sea, on the basis of a single specimen. It is characterised within the genus by a convex upper head profile; the posterior confluence of the frontal ridges slightly elevated at the nape, resulting in the presence of a slight sagittal crest; eye 5.2 times in head length; the lower hind margin of opercle slightly pointed in its lower half; the pelvic fins reduced to a scale-like structure with two soft rays on the posterior process of the basipterygium, its origin below the eighth dorsal-fin element; the first anal spine single, oval, scale like, and originating a short distance behind the vent (opposite the 34th dorsal-fin soft ray), anterior anal-fin soft rays minute and embedded, barely penetrating the skin and not visible externally, while the posterior fin supporting the rays enlarged and visible externally; approximately 17 anal-fin rays externally visible; approximately 83 dorsal-fin elements, with first spine not elongate, shorter than second; 12 pectoral-fin rays (ii + 6 + iv), with shorter anterior (fourth ray shortest) and longer posterior rays extending above the lateral line; 10 upper and 13 lower gill rakers of the first gill arch; head and body silver white, with a blackish margin anteriorly on snout and head, continuing along the anterior half of the dorsal-fin base. The new finding represents a new record of the genus from the Red Sea.     

Predicting the potential habitat of the harmful cyanobacteria Lyngbya majuscula in the Canary Islands (Spain)

This study presents the ecological niche and the potential distribution of Lyngbya majuscula in the Canary Islands (Spain) based on a bloom of this species on the eastern side of the Canarian Archipelago, in the Marine Reserve of La Graciosa (MRG). This finding represents the first L. majuscula bloom recorded in waters around the Canary Islands and this side of the Atlantic Ocean. The modeled suitability map revealed a potential distribution of L. majuscula in rocky and sandy habitats within shallow and sheltered areas exposed to sedimentation; where L. majuscula blooms had not previously been reported. The L. majuscula bloom detected in MRG is affecting rocky and sandy communities in this area. The possible expansion of these blooms may have harmful effects on important communities in the Canary Islands, including some of high ecological importance such as the Cymodocea nodosa meadows. Results of the L. majuscula distribution model presented here can be used to develop management strategies that avoid or minimize the risk of future bloom occurrences or expansions and their negative effects on the environment. The causes of L. majuscula blooms in MRG are being investigated.