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SummaryHormaomycin (HRM) is a structurally remarkable peptide produced by Streptomyces griseoflavus W-384 that acts as a Streptomyces signaling metabolite and exhibits potent antibiotic activity against coryneform actinomycetes. HRM biosynthetic studies have been hampered by inconsistent and low production. To enhance fermentation titers, the role of its cluster-encoded regulatory genes was investigated. Extra copies of the putative regulators hrmA and hrmB were introduced into the wild-type strain, resulting in an increase of HRM production and its analogs up to 135-fold. For the HrmB overproducer, six bioactive analogs were isolated and characterized. This study demonstrates that HrmA and HrmB are positive regulators in HRM biosynthesis. A third gene, hrmH, was identified as encoding a protein capable of shifting the metabolic profile of HRM and its derivatives. Its manipulation resulted in the generation of an additional HRM analog.

Investigations of heterochiral oligodeoxynucleotides 50-TD1GD2GD3- 30-30-GL3GL2TL1-50 (L33) and 30-TD1GD2GD3-50-50-GL3GL2TL1-30 (L55) forming quadruplex structures are reported. Data indicate the presence of enantiomeric left- and right-handed quadruplex helices. In the case of L55, NMR experiments point to an unusual equilibrium between them.

Sponge symbionts are a largely unexplored source of new and unusual metabolic pathways. Insights into the distribution and function of metabolic genes of sponge symbionts are crucial to dissect and exploit their biotechnological potential. Screening of the metagenome of the marine sponge Plakortis simplex led to the discovery of the swf family, a new group of mono-modular type I polyketide synthase/fatty acid synthase (PKS/FAS) specifically associated with sponge symbionts. Two different examples of the swf cluster were present in the metagenome of P. simplex. A third example of the cluster is present in the previously sequenced genome of a poribacterium from the sponge Aplysina aerophoba but was formerly considered orthologous to the wcb/rkp cluster. The swf cluster was also found in six additional species of sponges. Therefore, the swf cluster represents the second group of mono-modular PKS, after the supA family, to be widespread in marine sponges. The putative swf operon consists of swfA (type I PKS/FAS), swfB (reductase and sulphotransferase domains) and swfC (radical S-adenosylmethionine, or radical SAM). Activation of the acyl carrier protein (ACP) domain of the SwfA protein to its holo-form by co-expression with Svp is the first functional proof of swf type genes in marine sponges. However, the precise biosynthetic role of the swf clusters remains unknown., Environmental Microbiology Reports, 5 (6), ISSN:1758-2229

Clathramide A ( 1a ) and B ( 1b ) are two novel isomeric bromopyrrole alkaloids containing the uncommon N-methylimidazolinium moiety, isolated from the Caribbean sponge Agelas clathrodes . Their structures, elucidated on the basis of a detailed spectroscopic analysis, appear not biosynthetically related to oroidin and its derivatives. In addition, 1a-1b exhibited a mild antifungal activity tested in an agar disk assay on Aspergillus niger .

The GSL composition of the marine sponge Agelas dispar was investigated. In addition to four GSLs previously isolated from Agelas clathrodes (2 and 4), Agelas conifera (3), and Agelas longissima (5), the novel triglycosylceramide 1a was isolated as a major component of the GSL mixture. All the isolated GSLs were tested using the MLR assay, and only some of them were shown to be immunoactivating agents, suggesting a possible structure-activity relationship.

A specimen of the marine sponge Agelas longissima was analyzed for glycosphingolipids. Three cerebrosides 1a-3a were isolated, each as a mixture of homologs. The structure of the new glycosphingolipid 1a was elucidated by extensive NMR studies of its peracetate derivative and chemical analysis. Compound 2a, previously isolated from another specimen of A. longissima, exhibits in the new specimen a remarkably different alkyl chain composition.

Agelongine ( 1 ), a novel bromopyrrole alkaloid containing a pyridinium ring in place of the imidazole nucleus, usually found in Agelas alkaloids, has been isolated from the Caribbean sponge Agelas longissima , and its structure established by spectroscopic analysis and chemical degradation. Agelongine exhibited an antiserotonergic activity tested in vitro on the rat stomach fundus strip.

Simplexide is a glycolipid of marine origin, endowed with immunological properties, composed of a long chain secondary alcohol glycosylated by an α- d -glucosyl-(1→4)-β- d -galactosyl disaccharide residue. Herein we describe the preparation of a fluorescent derivative of simplexide, labeled at position 6 of the distal glucose with a dansyl group, as a probe for future studies on the mechanism by which simplexide affects the immune system. Fluorescent simplexide was prepared from a 6″-amino functionalized compound, which in turn was obtained through a highly efficient glycosylation between the preformed activated disaccharide and the long chain secondary alcohol 18-pentatriacontanol.

Plakohopanoid (3a), a new type of hopanoid derivative composed of a C32 hopanoid acid ester linked to a mannosyl-myo-inositol, was isolated from the sponge Plakortis cf. lita as its peracetyl derivative 3b. The structure of 3b was determined by a combination of spectroscopic analysis and micro-scale chemical degradation. Even though plakohopanoid was isolated from a sponge, its component parts are clearly of bacterial origin, and its bacterial biosynthesis is very likely. Until now, C32 hopanoic acids have been considered to be geohopanoids, i.e., diagenetic products that are formed through abiotic degradation of the biohopanoids present in bacteria. The presence of 3a in a marine living organism shows that there is a biosynthetic pathway to C32 hopanoic acids, and these substances should therefore no longer with certainty be considered to be geohopanoids.

Ring strain causes planar chirality in tedarenes A and B, two cyclic diarylheptanoids isolated from the marine sponge Tedania ignis. In both molecules, the chiral plane is an olefinic system, which is very rare among natural products. In tedarene A (1), interconversion is too fast to allow isolation of the enantiomeric atropisomers but still slow enough to cause coalescence of some (1)H and (13)C NMR signals at room temperature. In tedarene B (2), which also shows stable central and axial chirality, the two planar diastereomers are in slow equilibrium. Tedarene B is the smallest natural product with central, axial, and planar chirality in the same simple molecule. The identification of planar chirality as the difference between its conformational isomers allowed the use of theoretical prediction of the CD spectrum to determine the absolute configuration of the stereogenic carbon C-9 as well as of the biphenyl chiral axis.

CD and NMR studies on heterochiral oligodeoxynucleotides (d/l-ODNs) forming quadruplex structures are reported. Heterochiral ODNs, based on sequence TGGGGT, are able to form stable either right- or left-handed quadruplexes depending on d/l ratio and residues position. Results suggest that the 3′-end and the core of the G-run are more important than the 5′-end in determining the quadruplex handness. Particularly, oligonucleotide T DG DG LG LG DT D (L34) at low temperatures forms a well-defined left-handed quadruplex, notwithstanding it is mostly composed by natural d residues. This structure is characterized by three all-anti G-tetrads and one all-syn G-tetrad. © 2011 Elsevier Masson SAS. All rights reserved.

The new pigment “moraxanthin” was found in natural samples from a fish mortality site in the Inland Bays of Delaware, USA. Pure cultures of the species, tentatively named Chattonella cf. verruculosa, and natural samples contained this pigment as a dominant carotenoid. The pigment, obtained from a 10 L culture of C. cf. verruculosa, was isolated and harvested by HPLC and its structure determined from MS and 1D- and 2D-NMR. The data identified this pigment as a new acylated form of vaucheriaxanthin called moraxanthin after the berry like algal cell. Its presence in pure cultures and in natural bloom samples indicates that moraxanthin is specific to C. cf. verruculosa and can be used as a marker of its presence when HPLC is used to analyze natural blooms samples.

The application of the Wittig reaction to prepare chain-extended polyols starting from protected 2-deoxysugars has been investigated. The standard conditions cause alcohol elimination from the deoxysugar, leading to a diene. Triphenyl and tributyltin halides have been found to prevent alcohol elimination, so that the expected alkene is produced.

Trans-AT polyketide synthases (PKSs) are a recently discovered group of biosynthetic enzymes present in many bacteria. A strategy for the prediction of natural product structures from trans-AT PKS sequences was demonstrated to be a useful approach for the targeted isolation of bioactive polyketides from chemically poorly studied prokaryotic phyla, as exemplified by the elansolid-type antibiotics.

Two related peptide metabolites, one a cyclic depsipeptide, hoiamide B (2), and the other a linear lipopeptide, hoiamide C (3), were isolated from two different collections of marine cyanobacteria obtained in Papua New Guinea. Their structures were elucidated by combining various techniques in spectroscopy, chromatography, and synthetic chemistry. Both metabolites belong to the unique hoiamide structural class, characterized by possessing an acetate extended and S-adenosyl methionine modified isoleucine unit, a central triheterocyclic system comprised of two alpha-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C-15 polyketide unit. In neocortical neurons, the cyclic depsipeptide 2 stimulated sodium influx and suppressed spontaneous Ca(2+) oscillations with EC(50) values of 3.9 microM and 79.8 nM, respectively, while 3 had no significant effects in these assays.

Tedanol, a new brominated and sulfated pimarane diterpene was isolated from the Caribbean sponge Tedania ignis. Structure of tedanol was elucidated by mass spectroscopy and extensive NMR studies (including spectral simulation), and its absolute configuration was determined using the Mosher method. Tedanol showed a potent anti-inflammatory activity at 1 mg/kg evaluated in vivo in a mouse model of inflammation. After a single intraperitoneal administration, tedanol significantly reduced both the acute and the subchronic phases of carrageenan-induced inflammation. The anti-inflammatory activity was coupled with a strong inhibition of COX-2 expression, inhibition of cellular infiltration measured as mieloperoxidase (MPO) levels, and inhibition of iNOS expression. These features make tedanol a promising template for the development of new anti-inflammatory molecules with low gastrointestinal toxicity.

1H-1H scalar coupling across two stacked (parallel and eclipsed) aromatic rings has been revealed through the 1D and 2D 1H NMR analysis of a [2,2]paracyclophane and rationalized by means of density functional theory (DFT) calculation of the J values.

The solid state structure of the Zn-complex of clathridine (1), a genuine metabolite of the sponge Clathrina clathrus, was established by X-ray diffraction analysis. In addition, the conformation of 1 in CDCl3 solution was investigated by NOE difference NMR experiments.

The total synthesis of 1-2-docosanoylamino-O-(2-O-methyl-α-D-galactopyranosyl)-1,3,4-octadecanetriol (2), a 2′-methoxy analog of the immunostimulating α-galactoglycosphingolipid 1, is reported. Stereoselective α-glycosylation of the azido precursor of sphingosine was successfully performed for the first time using an improved Mukaiyama reaction. When assayed in a 72 h splenocyte proliferation test, compound 2 was significantly less stimulatory than the non-methylated compound 1, suggesting that the galactose 2-OH group is essential for the immunostimulatory activity of α-Gal-GSLs. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

In addition to the previously reported bacteriohopanoids, the marine sponge Plakortis simplex was shown to contain large amounts of (32R,33S,34S)-32,35-anhydrobacteriohopanetetrol. The structure of this new bacteriohopanoid was determined by extensive NMR analysis, and further supports the hypothesized biosynthetic pathway to bacteriohopanoids. Altogether, the amounts of bacteriohopanoids in P. simplex is as high as 50% of sterols in weight, and these compounds could play a structural role in the sponge cell membranes. © 2001 Elsevier Science Ltd.

new diterpene with the dolabellane skeleton 1 has been isolated from the sponge of the Indian Ocean, Sigmosceptrella quadrilobata. Its structure elucidation, including absolute stereochemistry, was performed with the aid of MS, NMR, and CD data and by molecular modeling. Compound 1 is moderately cytotoxic against four tumor cell lines.

Three new 9,11-secosterols, 3 beta,6 alpha,11-trihydroxy-9,11-seco-5 alpha-cholest-7-ene-9-one (1), 24S- (2a), and 24R-methyl-3 beta,6 alpha, 11-trihydroxy-9,11-seco-5 alpha-cholest-7,22E-diene-9-one (2b), were isolated from the Indian Ocean gorgonia, Subergorgia suberosa. Their structures were established by spectroscopic data.

Dimethyl 2-phenylseleno fumarate 1 acts as a strong Michael acceptor of amines, providing the corresponding 2-phenylseleno-3-amino succinates 2a and 2b in very high yields with complete regio-and good diastereoselectivity. (C) 1997 Elsevier Science Ltd.

We have developed a simple picomole (low nanogram) scale HPLC scheme which can separate all eight isomers of sphingosine and dihydrosphingosine thus leading to the identification of their relative and absolute configurations. The amino group of the sample is derivatized to its fluorescent N-naphthimide which is analyzed by normal and chiral phase HPLC, coupled with fluorescence peak detection. If necessary, the results of this HPLC method can be further corroborated by measurements of circular dichroic (CD) spectra of the N-naphthimido-derivatives and/or N,O-chromophoric derivatives. Copyright (C) 1996 Elsevier Science Ltd

An examination of the sterol mixture of the sponge Axinella proliferans collected in the Indian Ocean led to the isolation of nine A-nor-sterols, including two rare nor-sterols with a D-ring unsaturation. The known 3β-(hydroxymethyl)-A-nor-5α-cholest-15-ene has been identified by a comparison with mass spectrum and 1H and 13C nuclear magnetic resonance (NMR) data of the sterol isolated from Homoaxinella trachys, a marine sponge collected in the Indian Ocean. A new sterol, 3β-(hydroxymethyl)-A-nor-5α-cholest-14-ene-16α-ol, has been identified by their mass and two-dimensional NMR spectra compared with those of the D-ring unsaturated sterol, 5α-cholest-14-ene-3β,16α-diol isolated from the Mediterannean sponge Topsentia aurantiaca.

The sterol composition of the Caribbean sponge Neofibularia nolitangere has been investigated. In addition to usual sterols this sponge elaborates comparable amounts of 24-methylene-4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol (1), which is very unusual among sponge sterols, and lesser quantities of two new polyoxygenated sterols, (24S)-24-ethyl-5 alpha-cholest-8-ene-5,6 beta,7 alpha-triol (2) and (24S)-24-ethyl-5 alpha-cholest-8(14)-ene-5,6 beta,7 alpha-triol (3).

A purine derivative. 3,7-dimethylisoguanine ( 1 ), and a novel alkaloid with the unusual pyrrolopiperazine nucleus, longamide ( 2 ), were isolated from the sponge Agelas longissima , and their structures established on the basis of spectroscopic data. In addition, 2 exhibited a mild antibacterial activity.

The organic extract from Oceanapia bartschi has been shown to contain the antibiotic diterpene Ambliol A (1) and three indole derivatives, 3-bromoindole (2), 6-bromo-3-indolecarboxyaldehyde (3), and 6-bromo-5-hydroxy-3-indolecarboxyaldehyde (4). The structure of the novel compound 4 has been established from its spectroscopic (1H and 13C NMR, UV, IR, and MS) data

Ether glycolipids, which are mainly distributed among bacteria and mammalians, are characterized by the presence of 1 or 2 aIkyl chains, linked by ether bonds to position 1, 2 or 3. and a carbohydrate moiety (most often galactose) Iinked glycosidically to one of the hydroxy groups of glycerol. From Trikentrion loeve Carter, a sponge collected along the coast of Senegal. we have now isolated a new ether glycolipid, which is quite different from known compounds of this kind for the nature of the sugars and for the number of hydroxy groups involved in the glycosidic linkages.

Four new oxygenated diterpenes 1-4 were isolated from the Caribbean sponge Myrmekioderma styx. The structures of these compounds were deduced by ms, uv, ir, 1 H-and 13 C-nmr 1 H- 1 H COSY, XHCORR, and COLOC experiments. Compounds 1-4 are lethal to brine shrimp (Artemia salina)

The diarrethic shellfish poisoning from mussels, collected in the main producing areas in the seawater off the coast of Emilia-Romagna (Italy), has been investigated. The ether soluble material from hepatopancreas of highly toxic mussels (Mytilus galloprovincialis) was partitioned between n-hexane and methanol-water 9:1. The hydromethanolic phase was successively subjected to repeated chromatographic separations (SiO2, Sephadex LH-20 and reversed-phase HPLC). Following the toxicity of each fraction by mouse lethality test, the presence of okadaic acid has been evidenced through 1H NMR spectroscopy. The investigation of two further toxic fractions is still in progress. The obtained results represent an initial contribution to current Italian legislation and to future health measures to be defined at European Community level.

Haliclonol (2), a unique hydroxylated tyetrahydropyranone, was isolated from the Caribbean sponge Haliclona hogarthi, and its structure, including absolute stereochemistry, was elucidated by spectroscopic (ir, nmr, ms and cd) data

The hydrophilic extract of the Senegalese sponge Ptilocaulis spiculifer has been analyzed. It has been shown to contain dakaramine (1), a new tyrosine derivative containing iodine, an unusual feature for sponge metabolites. In addition, the new alkyl sulfate 2 (as a counterion of 1) and the known ecdysonic sterol 3 were isolated from the same extract.

The structure of an imidazole-containing compound, clathridine ( 1 ), was established from chemical evidence and by extensive NMR analysis. Clathridine was isolated from the sponge Clathrina clathrus and exhibited antimycotic activity. The sponge also contains smaller quantities of a Zn-complex of clathridine ( 4 ), which has been identified on the basis of its spectroscopic properties and synthesized from 1 with ZnSO 4 . A hypothesis for the stereostructure of 4 is also given.