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Under the guidance of global natural product social molecular networking, three new indolocarbazoles named streptocarbazoles F–H (1-3), along with staurosporine (4) were isolated from the marine-derived Streptomyces sp. OUCMDZ-5380. Structures of streptocarbazoles F–H were, respectively, determined as N-demethyl-N-hexanoylstaurosporine (1), N-demethyl-N-(2-methyl-3-methoxypyridin-4-yl) staurosporine staurosporine (2), and 4-(N-demethylstaurosporine-N-yl)-1,2-dimethyl-3-methoxypyridinium (3) by spectroscopic analysis and electronic circular dichroism comparison with staurosporine. Compared with staurosporine (4), streptocarbazoles F–H (1-3) showed a selective antiproliferation of the acute myeloid leukemia cell line MV4-11 with the IC50 values of 0.81, 0.55, and 1.88 μM, respectively.

One new (1) and fifteen known (2–16) p-terphenyls were isolated from a solid culture of the endophytic fungus Aspergillus sp. GZWMJZ-055 by adding the leaves of its host Eucommia ulmoides. Furthermore, nine p-terphenyls (17–25) were synthesized from the main compounds (5–7), among which derivatives 18, 19, 21, 22, and 25 are new p-terphenyls. Compounds 15 and 16 were also, respectively, synthesized from compounds 6 and 7 by oxidative cyclization of air in the presence of silica gel. These p-terphenyls especially those with 4,2′,4″-trihydroxy (4–7, 20, 21) or 4, 4″-dihydroxy-1,2,1′,2′-furan (15, 16) substituted nucleus, exhibited significant antioxidant and α-glucosidase inhibitory activities and lower cytotoxicity to caco-2 cells. The results indicated their potential use as lead compounds or dietary supplements for treating or preventing the diabetes.

Despite being potentially useful extremophile resources, there have been few reports on acid-tolerant fungi and their bioactive metabolites. Acidophilic/aciduric fungi (n = 237) were isolated from Thai mangrove sediments in an acidic medium. Using fungal identification technology (including morphologic observation, chemical screening, and sequence comparisons) all the isolates were identified and 41 representative isolates were selected for analysis of the phylogenetic relationships (ITS rDNA, β-tubulin, calmodulin, and actin gene sequences). There were seven genera identified – Penicillium; Aspergillus; Talaromyces; Cladosporium; Allophoma; Alternaria; and Trichoderma – in four taxonomic orders of the phylum Ascomycota, and Penicillium, Aspergillus, and Talaromyces were the dominant genera. Acidity tolerance was evaluated and 95% of the isolates could grow under extremely acidic conditions (pH 2). Six strains were classed as acidophilic fungi that cannot survive under pH 7, all of which had an extraordinarily close genetic relationship and belonged to the genus Talaromyces. This is the first report on the acidophilic characteristics of this genus. The antimicrobial, anti-tumor, and antiviral activities of the fermentation extracts were evaluated. Nearly three-quarters of the extracts showed cytotoxic activity, while less than a quarter showed antimicrobial or anti-H1N1 activity. The typical aciduric fungus Penicillium oxalicum OUCMDZ-5207 showed similar growth but completely different chemical diversity at pH 3 and 7. The metabolites of OUCMDZ-5207 that were obtained only at pH 3 were identified as tetrahydroauroglaucin (1), flavoglaucin (2), and auroglaucin (3), among which auroglaucin showed strong selective inhibition of A549 cells with an IC50 value of 5.67 μM. These results suggest that acid stress can activate silent gene clusters to expand the diversity of secondary metabolites, and the bioprospecting of aciduric/acidophilic microorganism resources in Thai mangrove sediments may lead to the discovery of compounds with potential medicinal applications.

The global shrimp industry has suffered bacterial diseases caused mainly by Vibrio species. The typical vibriosis, acute hepatopancreatic necrosis disease (AHPND), has resulted in mass mortality and devastating economic losses. Thus, therapeutic strategies are highly needed to decrease the risk of vibriosis outbreaks. Herein, we initially identified that the growth of the causative agent of AHPND, Vibrio parahaemolyticus (VPAHPND) and other vibrios in Pacific white shrimp (Litopenaeus vannamei) was inhibited by a Bacillus subtilis strain BSXE-1601. The natural products amicoumacins A, B, and C were purified from the cell-free supernatant from the strain BSXE-1601, but only amicoumacin A was demonstrated to be responsible for this anti-Vibrio activity. Our discovery provided the first evidence that amicoumacin A was highly active against shrimp pathogens, including the representative strain VPAHPND. Furthermore, we elucidated the amicoumacin A biosynthetic gene cluster by whole genome sequencing of the B. subtilis strain BSXE-1601. In addition to amicoumacin A, the strain BSXE-1601 genome harbored other genes encoding bacillibactin, fengycin, surfactin, bacilysin, and subtilosin A, all of which have previously reported antagonistic activities against pathogenic strains. The whole-genome analysis provided unequivocal evidence in support of the huge potential of the strain BSXE-1601 to produce diverse biologically antagonistic natural products, which may facilitate further studies on the effective therapeutics for detrimental diseases in shrimp.

A novel actinobacterium, strain HNM0039T, was isolated from a marine sponge sample collected at the coast of Wenchang, Hainan, China and its polyphasic taxonomy was studied. The isolate had morphological and chemical characteristics consistent with the genus Streptomyces. Based on the 16S rRNA gene sequence analysis, strain HNM0039T was closely related to Streptomyces wuyuanensis CGMCC 4.7042T (99.38%) and Streptomyces spongiicola HNM0071T (99.05%). The organism formed a well-delineated subclade with S. wuyuanensis CGMCC 4.7042T and S. spongiicola HNM0071T in the Streptomyces 16S rRNA gene tree. Multi-locus sequence analysis (MLSA) based on five house-keeping gene alleles (atpD, gyrB, rpoB, recA, trpB) further confirmed their relationship. DNA–DNA relatedness between strain HNM0039T and its closest type strains, namely S. wuyuanensis CGMCC 4.7042T and S. spongiicola HNM0071T, were 46.5 and 45.1%, respectively. The average nucleotide identity (ANI) between strain HNM0039T and its two neighbor strains were 89.65 and 91.44%, respectively. The complete genome size of strain HNM0039T was 7.2 Mbp, comprising 6226 predicted genes with DNA G+C content of 72.46 mol%. Thirty-one putative secondary metabolite biosynthetic gene clusters were also predicted in the genome of strain HNM0039T. Among them, the tirandamycin biosynthetic gene cluster has been characterized completely. The crude extract of strain HNM0039T exhibited potent antibacterial activity against Streptococcus agalactiae in Nile tilapia. And tirandamycins A and B were further identified as the active components with MIC values of 2.52 and 2.55 μg/ml, respectively. Based on genotypic and phenotypic characteristics, it is concluded that strain HNM0039T represents a novel species of the genus Streptomyces whose name was proposed as Streptomyces tirandamycinicus sp. nov. The type strain is HNM0039T (= CCTCC AA 2018045T = KCTC 49236T).

In the process of profiling the secondary metabolites of actinobacteria isolated from the Saudi coastal habitats for production of antibiotics and anti-cancer drugs, the cultures of strain WH1 that was identified as Streptomyces heliomycini exhibited strong antibacterial activity against Staphylococcus aureus. By means of MS and NMR techniques, the active compounds were characterized as actinomycins X0β, X2, and D, respectively. The research on the productivity of this strain for actinomycins revealed that the highest production of actinomycins X0β, X2, and D was reached in the medium MII within 5% salinity and pH 8.5. In this optimized condition, the fermentation titers of actinomycins X0β, X2, and D were 107.6 ± 4.2, 283.4 ± 75.3, and 458.0 ± 76.3 mg/L, respectively. All the three actinomycins X0β, X2, and D showed potent cytotoxicities against the MCF-7, K562, and A549 tumor cell lines, in which actinomycin X2 was the most active against the three tumor cell lines with the IC50 values of 0.8–1.8 nM. Both actinomycins X2 and D showed potent antibacterial activities against S. aureus and the methicillin-resistant S. aureus, Bacillus subtilis, and B. cereus and the actinomycin X2 was more potent.