This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci.

Two new (1, 2 viz Rubracin D and E) and sixteen known Glyceroglycolipids (3–18) in the saprophytic fungus Tubeufia rubra (PF02-2) from decaying wood in freshwater habitat were isolated and identified. Their chemical structures were elucidated via means of the extensive spectroscopic analyses of NMR, HR-ESI-MS and UV spectra, as well as comparison with literature data. The new compounds were assayed for the reversal activity of multidrug resistance (MDR) on MCF-7/ADM, K562/ADM and A549/ADM cell lines, and both compounds 1 and 2 reversed MDR in the three resistant cancer cell lines with concentration dependence. In the assay on K562/ADM, both new compounds had been proved to have remarkable MDR reversal effects, which were higher than those of the positive control viz Verapamil (Vrp). Meanwhile, in the assay on A549/ADM, compound 1 displayed significant MDR reversal effects, which were also higher than those of Vrp at certain concentrations. Furthermore, the Western blot assay proved that both new compounds reversed the MDR in the resistant cancer cell line viz MCF-7/ADM by inhibiting the overexpression of P-glycoprotein. This is the first report that the Glyceroglycolipids isolated firstly from the fungal genus Tubeufia reversed MDR in resistant cancer cells.

AA chemical investigation of secondary metabolites from the saprobic fungus Tubeufia rubra led to isolation of a novel nitrogen-containing glyceride, Rubracin A (1), and a novel eight-membered cyclic ether carboxylate methyl ester, Rubracin H (2). Together with six known compounds (3-8). The chemical structure of these new compounds were elucidated by 1D and 2D NMR and HR-ESI-MS techniques. Although, there are no observed cytotoxic effects of compound 1 against MCF-7/Dox, A549/Dox, and K562/Dox cells at oncentrations below 25 μg/mL, usage of compound 1 and doxorubicin revealed the MDR reversal via decreased IC50 values than that of sole doxorubicin application in the cell lines. A preliminary Western Blot assay indicated that the MDR reversal of compound 1 was due to suppression of P-glycoprotein (P-gp) expression.

Seven new clerodane diterpenoids, dysoxydensins A–G (1–7), together with six known clerodanes, were isolated from Dysoxylum densiflorum. The structures of all the compounds were elucidated by extensive spectroscopic analysis. These compounds were evaluated for their cytotoxic activities against five human cancer cell lines, and compounds 2, 3, and 5 showed moderate cytotoxic activities. ^* These authors contributed equally to this work.

Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis.