Antimicrobial Polyketides from the Marine-Derived Fungus Spiromastix sp. SCSIO F190.

Three diphenyl ethers (1-3) and a cyclopentenone (4), together with seven known compounds (5-11), were isolated from the fermentation broth of the marine sediment-derived fungus Spiromastix sp. SCSIO F190. Compounds 3 and 4 were found to exist as a pair of atropisomers (3a, 3b) and racemates (4a, 4b), respectively. The planar structures of compounds 1-4 were elucidated on the basis of NMR and HRESIMS data sets. The absolute configurations of 2 and 3 were determined by spectroscopic and single-crystal X-ray diffraction analyses, whereas the configuration of 4 was determined by spectroscopic and chiral analyses. All compounds, except for 4 and 11, displayed activities against various pathogenic bacteria. Notably, compounds 1-4, especially 1, exhibited strong activity against Gram-positive bacteria, including methicillin-resistant bacterial strains of Staphylococcus aureus (MRSA), Enterococcus faecalis ATCC 29212, and Bacillus subtilis BS01, with MIC values ranging from 0.5 to 4 µg/mL. Moreover, the structure-activity relationship analyses of the active compounds and their analogues revealed the critical structural features correlating to the observed antimicrobial activities, herein providing insights for antimicrobial drug development.

OSMAC-Based Discovery and Biosynthetic Gene Clusters Analysis of Secondary Metabolites from Marine-Derived Streptomyces globisporus SCSIO LCY30.

The one strain many compounds (OSMAC) strategy is an effective method for activating silent gene clusters by cultivating microorganisms under various conditions. The whole genome sequence of the marine-derived strain Streptomyces globisporus SCSIO LCY30 revealed that it contains 30 biosynthetic gene clusters (BGCs). By using the OSMAC strategy, three types of secondary metabolites were activated and identified, including three angucyclines, mayamycin A (1), mayamycin B (2), and rabolemycin (3); two streptophenazines (streptophenazin O (4) and M (5)); and a macrolide dimeric dinactin (6), respectively. The biosynthetic pathways of the secondary metabolites in these three families were proposed based on the gene function prediction and structural information. The bioactivity assays showed that angucycline compounds 1-3 exhibited potent antitumor activities against 11 human cancer cell lines and antibacterial activities against a series of Gram-positive bacteria. Mayamycin (1) selectively exhibited potent cytotoxicity activity against triple-negative breast cancer (TNBC) cell lines such as MDA-MB-231, MDA-MB-468, and Bt-549, with IC50 values of 0.60-2.22 µM.

Characterization of the Glycosyltransferase and Methyltransferase Encoded Remotely from the Actinopyrone Biosynthetic Gene Cluster Enables Access to Diverse Analogues.

The actinopyrone biosynthetic gene cluster (atpn) lacks glycosyl- and methyltransferase genes, yet its product clearly calls for such enzymes. Using bioinformatics and biochemical methods, we confirmed that the mt3913 and gt723 genes, well beyond the atpn cluster boundaries, encode methyltransferase and glycosyltransferase, respectively. Moreover, homologous protein GT1507 enabled us to produce 14 non-natural actinopyrone analogues. PM050463 (3) was found to display potent anti-Helicobacter pylori activity and no signs of cytotoxicity.

The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets.

Neuroblastoma (NB) is a malignant tumor in young children that originates from the neural crest of the sympathetic nervous system. Generally, NB occurs in the adrenal glands, but it can also affect the nerve tissues of the neck, chest, abdomen, and pelvis. Understanding the pathophysiology of NB and developing novel therapeutic approaches are critical. Noncoding RNAs (ncRNAs) are associated with crucial aspects of pathology, metastasis and drug resistance in NB. Here, we summarized the pretranscriptional, transcriptional and posttranscriptional regulatory mechanisms of ncRNAs involved in NB, especially focusing on regulatory pathways. Furthermore, ncRNAs with the potential to serve as biomarkers for risk stratification, drug resistance and therapeutic targets are also discussed, highlighting the clinical application of ncRNAs in NB.