Soleiman E. Helaly

Plantazolicin A and B: Structure Elucidation of Ribosomally Synthesized Thiazole/Oxazole Peptides from Bacillus amyloliquefaciens FZB42

The structures of the ribosomally synthesized peptide antibiotics from Bacillus amyloliquefaciens FZB42, plantazolicin A and B, have been elucidated by high resolving ESI-MSMS, 2D (1)H-(13)C-correlated NMR spectroscopy as well as (1)H-(15)N-HMQC/(1)H-(15)N-HMBC NMR experiments. (15)N-labeling prior to the experiments facilitated the structure determination, unveiling a hitherto unusual number of thiazoles and oxazoles formed from a linear 14mer precursor peptide. This finding further extends the number of known secondary metabolites from B. amyloliquefaciens and represents a new type of secondary metabolites from the genus Bacillus.

Atacamycins A–C, 22-membered antitumor macrolactones produced by Streptomyces sp. C38*

Three new 22-membered macrolactone antibiotics, atacamycins A–C, were produced by Streptomyces sp. C38, a strain isolated from a hyper-arid soil collected from the Atacama Desert in the north of Chile. The metabolites were discovered in our HPLC-diode array screening and isolated from the mycelium by extraction and chromatographic purification steps. The structures were determined by mass spectrometry and NMR experiments. Atacamycins A, B and C exhibited moderate inhibitory activities against the enzyme phosphodiesterase (PDE-4B2), whereas atacamycin A showed a moderate antiproliferative activity against adeno carcinoma and breast carcinoma cells.

Elaiomycins B and C: alkylhydrazide antibiotics from Streptomyces sp. BK 190.

Two novel alkyhydrazides, elaiomycins B and C, together with the azoxy antibiotic elaiomycin were isolated from Streptomyces sp. BK 190. The structures were established by 1D- and 2D-NMR spectroscopy including (15)N NMR studies and high-resolution orbitrap-ESI-mass spectrometry.

Pyristriatins A and B: Pyridino-Cyathane Antibiotics from the Basidiomycete Cyathus cf. striatus

Two novel pyridino-cyathane diterpenoids, pyristriatins A and B (1 and 2), together with striatin C (3) were isolated from cultures of Cyathus cf. striatus, a basidiomycete that was found during a field trip in northern Thailand. The pyristriatins showed antimicrobial effects against Gram-positive bacteria and fungi. The isolation, structure elucidation, relative configuration, and biological and cytotoxic activity are described. Their structures were assigned by HRMS and NMR spectroscopy. We also describe the first 2D NMR assignment of striatin C. Pyristriatins A and B are the first cyathane natural products featuring a pyridine ring.

Elaiomycins B and C, novel alkylhydrazides produced by Streptomyces sp. BK 190

Dereplicated novel actinomycetes from neglected habitats provide high quality biological material for screening programs designed to detect novel bioactive secondary metabolites.2 Such organisms include neutrotolerant acidophilic streptomycetes which grow from pH 4.5 to 7.5, with an optimum between pH 5.0 and 5.5.3 Members of this group were isolated from a hay meadow soil taken from Cockle Park Experimental Farm in Northumberland, UK. The isolates were grown as submerged cultures in complex media, and extracts from the culture filtrates and mycelia included in our HPLC-diode array screening program to detect novel secondary metabolites by means of an in-house HPLC-UV-Vis database, which contains approximately 950 natural products, mainly antibiotics.4 Strain BK 190 was of interest because of the presence of three prominent peaks in the HPLC profile of a culture filtrate extract. The strain was assigned to the genus Streptomyces by its morphological and chemotaxonomic properties.5 Strain BK 190 formed an extensively branched substrate mycelium, a grey aerial spore mass and aerial hyphae, which differentiated into spiral chains of smooth-surfaced spores on oatmeal agar, contained LL-diaminopimelic acid, galactose, glucose and xylose as major sugars, N-acetylated muramic acid, predominant amounts of hexa- and octa-hydrogenated menaquinones with nine isoprene units, and produced iso- and anteiso-branched fatty acids with C15:0 and iso-C16:0 as major components. The temperature and pH ranges for growth were 10–35 °C and pH 4.0–8.0, respectively. Phylogenetic analyses showed that the organism was most closely related to the type strain of Streptomyces sanglieri; the two organisms shared a 16S rRNA similarity of 99.9%, a value that corresponds to a single nucleotide difference at 1434 locations.

Gombapyrones, new α-pyrone metabolites produced by Streptomyces griseoruber Acta 3662

Gombapyrones A–D, new members of the α-pyrone family of secondary metabolites, were produced by Streptomyces griseoruber Acta 3662, which was isolated from bamboo tree rhizosphere. The strain was characterized by its morphological and chemotaxonomical features and by 16S rDNA sequencing as S. griseobuber. The gombapyrone structures were determined by mass spectrometry and by NMR experiments, and were found to have an inhibitory activity against protein tyrosine phosphatase 1B and glycogen synthase kinase 3β.

Langkolide, a 32-membered macrolactone antibiotic produced by Streptomyces sp. Acta 3062.

A new 32-membered macrolactone antibiotic, named langkolide, was isolated from the mycelium of Streptomyces sp. Acta 3062. The langkolide structure was determined by HR-MS and 1D and 2D NMR as a 32-membered macrolactone connected from an overhanging polyketide tail to a naphthoquinone unit mediated by two carbohydrate moieties. The producing strain was isolated from a rhizosphere soil of Clitorea sp. collected at Burau Bay, Langkawi, Malaysia, and was characterized by its morphological and chemotaxonomic features in addition to its 16S rRNA gene sequence. It was identified as a member of the Streptomyces galbus clade. Langkolide exhibited various bioactivities including antimicrobial and antiproliferative activities. Furthermore, langkolide inhibited human recombinant phosphodiesterase 4 with an IC(50) value of 0.48 μM.

Preussilides A–F, Bicyclic Polyketides from the Endophytic Fungus Preussia similis with Antiproliferative Activity

Six novel bioactive bicyclic polyketides (1-6) were isolated from cultures of an endophytic fungus of the medicinal plant Globularia alypum collected in Batna, Algeria. The producer organism was identified as Preussia similis using morphological and molecular phylogenetic methods. The structures of metabolites 1-6, for which the trivial names preussilides A-F are proposed, were elucidated using a combination of spectral methods, including extensive 2D NMR spectroscopy, high-resolution mass spectrometry, and CD spectroscopy. Preussilides were tested for antimicrobial and antiproliferative effects, and, in particular, compounds 1 and 3 showed selective activities against eukaryotes. Subsequent studies on the influence of 1 and 3 on the morphology of human osteosarcoma cells (U2OS) suggest that these two polyketides might target an enzyme involved in coordination of the cell division cycle. Hence, they might, for instance, affect timing or spindle assembly mechanisms, leading to defects in chromosome segregation and/or spindle geometry.

Warkmycin, a novel angucycline antibiotic produced by Streptomyces sp. Acta 2930

A novel angucycline-type antibiotic, warkmycin, was isolated from the culture filtrate of Streptomyces strain Acta 2930. Its chemical structure was elucidated by HR-MS, one-dimensional and 2D NMR experiments. The compound inhibits the growth of Gram-positive bacteria and shows a strong antiproliferative activity against mouse fibroblast cell line NIH-3T3 and human cancer cell lines HepG2 and HT29.

Ijuhya vitellina sp. nov., a novel source for chaetoglobosin A, is a destructive parasite of the cereal cyst nematode Heterodera filipjevi

Cyst nematodes are globally important pathogens in agriculture. Their sedentary lifestyle and long-term association with the roots of host plants render cyst nematodes especially good targets for attack by parasitic fungi. In this context fungi were specifically isolated from nematode eggs of the cereal cyst nematode Heterodera filipjevi. Here, Ijuhya vitellina (Ascomycota, Hypocreales, Bionectriaceae), encountered in wheat fields in Turkey, is newly described on the basis of phylogenetic analyses, morphological characters and life-style related inferences. The species destructively parasitises eggs inside cysts of H. filipjevi. The parasitism was reproduced in in vitro studies. Infected eggs were found to harbour microsclerotia produced by I. vitellina that resemble long-term survival structures also known from other ascomycetes. Microsclerotia were also formed by this species in pure cultures obtained from both, solitarily isolated infected eggs obtained from fields and artificially infected eggs. Hyphae penetrating the eggshell colonised the interior of eggs and became transformed into multicellular, chlamydospore-like structures that developed into microsclerotia. When isolated on artificial media, microsclerotia germinated to produce multiple emerging hyphae. The specific nature of morphological structures produced by I. vitellina inside nematode eggs is interpreted as a unique mode of interaction allowing long-term survival of the fungus inside nematode cysts that are known to survive periods of drought or other harsh environmental conditions. Generic classification of the new species is based on molecular phylogenetic inferences using five different gene regions. I. vitellina is the only species of the genus known to parasitise nematodes and produce microsclerotia. Metabolomic analyses revealed that within the Ijuhya species studied here, only I. vitellina produces chaetoglobosin A and its derivate 19-O-acetylchaetoglobosin A. Nematicidal and nematode-inhibiting activities of these compounds have been demonstrated suggesting that the production of these compounds may represent an adaptation to nematode parasitism.