Cysteine-Derived Pleurotin Congeners from the Nematode-Trapping Basidiomycete <i>Hohenbuehelia grisea</i>

The discovery of a <i>Hohenbuehelia grisea</i> specimen during a field trip in Northern Thailand led to the isolation and identification of three novel sulfur-bearing derivatives of dihydropleurotinic acid (<b>4</b>). Thiopleurotinic acid A (<b>1</b>) was established by the interpretation of spectral data (HRESIMS, 2D-NMR) as a 2-hydroxy-3-mercaptopropanoic acid conjugate of dihydropleurotinic acid. Thiopleurotinic acid B (<b>2</b>) was shown to be the <i>N</i>-acetylcysteine conjugate of <b>4</b>. A third compound (<b>3</b>) was established as a thiazole-containing derivative. Through feeding experiments with [U–¹³C₃, ¹⁵N]-l-cysteine the formation of all three metabolites was shown to involve cysteine condensation with <b>4</b>. The decreased cytotoxicity and antimicrobial activities of the new derivatives <b>1</b>–<b>3</b>, compared to the parent compound <b>4</b>, indicate a possible detoxification pathway of filamentous fungi

Sorazolons, Carbazole Alkaloids from <i>Sorangium cellulosum</i> Strain Soce375

Sorazolons A (<b>1</b>) to E2 (<b>9</b>) were isolated from <i>Sorangium cellulosum</i> strain Soce375. Their molecular structures were elucidated using extensive HRESIMS and NMR analysis. The absolute configuration of sorazolon A (<b>1</b>) was determined by comparison of the experimental CD spectrum with quantum chemical calculated spectra for both enantiomers. Sorazolons D2 (<b>7</b>), E (<b>8</b>), and E2 (<b>9</b>) exhibit a moderate cytotoxic activity against mouse fibroblast cell line L929 with IC₅₀ values between 5.0 μM and 0.09 mM

Additional file 5: of Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains

Mutacin overlay assay to determine the specificity of the sensor strains. Overnight cultures of wild-type and knock-out strains for mutacins of S. mutans UA159 were spotted on THBY agar and allowed to incubate for 4–6 h. The exponential cultures of indicator strains S. sanguinis and L. lactis were overlaid on the plates using 0.7% agar. The area of zone of inhibition was measured after 20 h of incubation. (TIFF 1398 kb

Production of Trichothecenes by the Apple Sooty Blotch Fungus Microcyclospora tardicrescens

The sooty blotch and flyspeck (SBFS) syndrome of apples and other fruits is caused by a complex consortium of epiphytic fungi that colonize the fruit cuticula. SBFS fungal strains isolated from apples were screened for growth inhibition of the phytopathogen Colletotrichum fioriniae in dual culture tests. Extracts of 11 isolates of SBFS fungi (Microcyclospora malicola, Microcyclospora pomicola, Microcyclospora tardicrescens, and Microcyclosporella mali) inhibited growth of the test strains and were studied for production of antibiotics. A strain of <i>Microcyclospora tardicrescens</i> strongly inhibited growth and was cultivated on a larger scale to characterize its secondary metabolites. Bioassay-guided fractionation and subsequent structure elucidation by spectroscopic and spectrometric methods (NMR, HRMS) yielded trichothecolone acetate (<b>1</b>) and its novel derivative (<i>S</i>)-7-hydroxytrichothecolone acetate (<b>2</b>) as active principles. <i>Microcyclospora tardicrescens</i> was thus identified as a producer of the hazardous trichothecene type mycotoxins for the first time, which should give reason to monitor these foodborne fungi more carefully in the future

Additional file 3: of Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains

Growth of S. mutans UA159 Δ423. Knock-out strains for mutacin encoding genes were created by replacing genes with erythromycin B cassette and the growth (OD 600) was monitored in THBY. Data show the mean and standard deviation of a biological replicate which were conducted with triplicate subsamples. (TIFF 848 kb

Indothiazinone, an Indolyl Thiazolyl Ketone from a Novel Myxobacterium Belonging to the Sorangiineae

Indothiazinone (<b>1</b>), an indolyl thiazolyl ketone, was discovered in cultures of novel myxobacterial strain 706, recently isolated from compost in Germany. Molecular phylogenetic studies based on 16S rRNA gene sequences revealed strain 706 to be a representative of a new family of the Sorangiineae. A screening of the culture broth for antimicrobial metabolites followed by isolation and characterization of these compounds revealed six indole derivatives and a 1,4-naphthoquinone derivative. The structures were determined to be indothiazinone (<b>1</b>; 1<i>H</i>-indol-3-yl­(1,3-thiazol-2-yl)­methanone) and three 3-methylbuta-1,3-dien-1-yl-substituted indoles, indolyl ethanol <b>2</b> and the <i>E</i>- and <i>Z</i>-isomers of indolyl ethylidenehydroxylamine <b>4</b> and <b>5</b> by MS and NMR spectroscopic analyses. In the indolyl ethanol derivative <b>3</b> the unsaturated methylene group of the butadienyl residue was replaced by an oxygen atom to give the keto group of the butanone side chain. Further 1<i>H</i>-indol-3-ylacetonitrile (<b>6</b>) was identified, which was already known as a myxobacterial metabolite. 2-Hydroxyethyl-3-methyl-1,4-naphthoquinone (<b>7</b>) was recognized during dereplication as an antibiotic previously isolated from <i>Actinoplanes capillaceus</i>. Whereas <b>1</b>, <b>4</b>, <b>5</b>, and <b>7</b> showed weak activity against yeasts and filamentous fungi, isomers <b>4</b> and <b>5</b> were weakly active against Gram-positive bacteria and mouse fibroblasts. Compound <b>6</b> is volatile, and <b>2</b> and <b>3</b> showed no activity in a number of assays

Additional file 1: of Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains

Primers used in this study and their use. (DOCX 16 kb

Pyrronazols, Metabolites from the Myxobacteria <i>Nannocystis pusilla</i> and <i>N. exedens</i>, Are Unusual Chlorinated Pyrone-Oxazole-Pyrroles

The chlorinated pyrrole-oxazole-pyrones pyrronazol A (<b>1</b>), pyrronazol A2 (<b>2</b>), and pyrronazol B (<b>3</b>) were isolated from <i>Nannocystis pusilla</i> strain Ari7, and two chlorinated pyrrole-oxazole isomers, pyrronazols C1 (<b>4</b>) and C2 (<b>5</b>), were isolated from <i>N. pusilla</i> strain Na a174. HRESIMS, NMR, and X-ray crystallographic analysis was used in the structure elucidation including the absolute configuration of pyrronazol A (<b>1</b>). In addition to pyrronazols, 1,6-phenazine-diol (<b>6</b>) and its glycosyl derivative, 1-hydroxyphenazin-6-yl-α-d-arabinofuranoside (<b>7</b>), were isolated and identified from the culture broth of <i>N. pusilla</i> strain Ari7. When tested for biological activity against bacteria, fungi, and yeasts, <b>1</b> showed weak antifungal activity against <i>Mucor hiemalis</i> (MIC 33.3 μg/mL) but no antibacterial activity, while <b>6</b> showed weak antibacterial and antifungal activity (MIC 33.3 μg/mL) against some of the strains tested. In cell culture experiments <b>1</b> showed no significant cytotoxicity, while <b>6</b> was active against several cell lines, especially the human ovarian carcinoma cells SK-OV-3 (LD₅₀ 2.59 μM)

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

Two novel pyridino-cyathane diterpenoids, pyristriatins A and B (<b>1</b> and <b>2</b>), together with striatin C (<b>3</b>) were isolated from cultures of <i>Cyathus</i> cf<i>. striatus</i>, 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

Deconins A–E: Cuparenic and Mevalonic or Propionic Acid Conjugates from the Basidiomycete <i>Deconica</i> sp. 471

Bioassay-guided fractionation of antibacterial extracts from cultures of a basidiomycete from Northern Thailand, which represents a new species of the genus <i>Deconica</i>, yielded the terpenoid deconin A (<b>1</b>), whose structure was elucidated by spectral methods (NMR, HRMS) as a cuparenic/mevalonic acid conjugate. The absolute configuration of <b>1</b> was determined after saponification and comparison of specific rotations of the resulting cuparenic acid and mevalonolactone with authentic standards and literature data. Six minor congeners (<b>2</b>–<b>7</b>) were isolated and identified, and their antimicrobial and cytotoxic effects are reported. Compounds <b>1</b>–<b>4</b> are the first natural products featuring an unmodified mevalonic acid residue as a building block