Search

Three new actinopyrone derivatives, actinopyrones E–G (1, 3, and 4), together with three known analogues, PM050463 (2), actinopyrone D (5), and PM050511 (6), were isolated from Streptomycessp. SCSIO ZS0520 derived from a deep-sea hydrothermal vent. Their structures, complete with absolute configurations, were elucidated using extensive spectroscopic analyses combined with Mosher’s method, ECD calculations, and bioinformatics analyses. These findings corrected the absolute configurations of previously reported actinopyrone analogues 2, 5, and 6at C-3, C-9, and C-10. Notably, compound 6displayed notable cytotoxicity against six human cell lines with IC50values of 0.26–2.22 μM. A likely biosynthetic pathway and annotations of protein function are proposed on the basis of bioinformatics analyses. Genes coding for methyltransferase and glycosyltransferase tailoring chemistries needed to generate final structures were notably absent from the biosynthetic gene cluster. Taken together, these results enable further bioengineering of the actinopyrones and related congeners as potential antitumor agents.

Eight new β-resorcylic acid lactones (RALs), including the hypothemycin-type compounds paecilomycins N–P (1–3) and the radicicol-type metabolites dechloropochonin I (4), monocillins VI (5) and VII (6), 4′-hydroxymonocillin IV (7), and 4′-methoxymonocillin IV (8), along with nine known RALs (9–17), were isolated from the cultures of Paecilomycessp. SC0924. Compounds 1and 2feature a novel 6/11/5 ring system, and 3is the first 5′-keto RAL. The structures of 1–8were elucidated on the basis of extensive spectroscopic analysis, X-ray diffraction analysis, and theoretical calculations of ECD spectra. Compounds 3, 5, and 6exhibit cytotoxicity against MCF-7, A549, and HeLa cells, and compounds 5and 7display antifungal activity against Peronophythora litchii.

Three new abyssomicin monomers designated neoabyssomicins D (1), E (2), and A2 (3) and the two dimeric neoabyssomicins F (4) and G (5) were discovered from the marine-derived Streptomyces koyangensisSCSIO 5802, and their structures rigorously elucidated. Neoabyssomicin D (1) possesses an unprecedented 8/5/5/7 ring skeleton, the biosynthesis of which (as well as 2) is proposed herein. Additionally, dimeric agents 4and 5were found to be active against methicillin-resistant Staphylococcus aureusand vesicular stomatitis virus, respectively.

Five new highly oxygenated α-pyrone merosesquiterpenoids, ochraceopones A–E (1–5), together with one new double bond isomer of asteltoxin, isoasteltoxin (6), and two known asteltoxin derivatives, asteltoxin (7) and asteltoxin B (8), were isolated from an Antarctic soil-derived fungus, Aspergillus ochraceopetaliformisSCSIO 05702. Their structures were determined through extensive spectroscopic analysis, CD spectra, quantum mechanical calculations, and X-ray single-crystal diffraction. Ochraceopones A–D (1–4) are the first examples of α-pyrone merosesquiterpenoids possessing a linear tetracyclic carbon skeleton, which has not been previously described. All the isolated compounds were tested for their antiviral, cytotoxic, antibacterial, and antitubercular activities. Among these compounds, ochraceopone A (1), isoasteltoxin (6), and asteltoxin (7) exhibited antiviral activities against the H1N1 and H3N2 influenza viruses with IC50values of >20.0/12.2 ± 4.10, 0.23 ± 0.05/0.66 ± 0.09, and 0.54 ± 0.06/0.84 ± 0.02 μM, respectively. A possible biosynthetic pathway for ochraceopones A–E (1–5) was proposed.

Paeciloketals (1–3), new benzannulated spiroketal derivatives, were isolated from the marine fungus Paecilomyces variotiiderived from the giant jellyfish Nemopilema nomurai. Compound 1was present as a racemate and was resolved into enantiopure 1aand 1bby chiral-phase separation on a cellulose column. Compounds 2and 3, possessing a novel benzannulated spiroketal skeleton, were rapidly interconvertible and yielded an equilibrium mixture on standing at room temperature. The relative and absolute configurations of compounds 2and 3were determined by NOESY analysis and ECD calculations. Compound 1showed modest antibacterial activity against the marine pathogen Vibrio ichthyoenteri.

Two new polycyclic tetramate macrolactams, lysobacteramides A (1) and B (2), together with HSAF (heat-stable antifungal factor, 3), 3-dehydroxy HSAF (4), and alteramide A (5) were isolated from a culture of Lysobacter enzymogenesC3 in nutrient yeast glycerol medium. Their structures were determined by MS and extensive NMR analysis. The absolute configurations of 1–5were assigned by theoretical calculations of their ECD spectra. Although HSAF and analogues were reported from several microorganisms, their absolute configurations had not been established. The isolation and the absolute configurations of these compounds revealed new insights into the biosynthetic mechanism for formation of the polycycles. Compounds 1–4exhibited cytotoxic activity against human carcinoma A549, HepG2, and MCF-7 cells with IC50values ranging from 0.26 to 10.3 μM. Compounds 2and 3showed antifungal activity against Fusarium verticillioideswith IC50value of 47.9 and 6.90 μg/mL, respectively.