Abstract:The mangrove ecosystem is a largely unexplored source for actinomycetes with the potential to produce biologically active secondary metabolites. Consequently, we set out to isolate, characterize and screen actinomycetes from soil and plant material collected from eight mangrove sites in China. Over 2,000 actinomycetes were isolated and of these approximately 20%, 5%, and 10% inhibited the growth of Human Colon Tumor 116 cells, Candida albicans and Staphylococcus aureus, respectively, while 3% inhibited protein tyrosine phosphatase 1B (PTP1B), a protein related to diabetes. In addition, nine isolates inhibited aurora kinase A, an anti-cancer related protein, and three inhibited caspase 3, a protein related to neurodegenerative diseases. Representative bioactive isolates were characterized using genotypic and phenotypic procedures and classified to thirteen genera, notably to the genera Micromonospora and Streptomyces. Actinomycetes showing cytotoxic activity were assigned to seven genera whereas only Micromonospora and Streptomyces strains showed anti-PTP1B activity. We conclude that actinomycetes isolated from mangrove habitats are a potentially rich source for the discovery of anti-infection and anti-tumor compounds, and of agents for treating neurodegenerative diseases and diabetes.

The platform consists of three modules, which are pre‐configured bioinformatic pipelines, cloud toolsets, and online omics' courses. The pre‐configured bioinformatic pipelines not only combine analytic tools for metagenomics, genomes, transcriptome, proteomics and metabolomics, but also provide users with powerful and convenient interactive analysis reports, which allow them to analyze and mine data independently. As a useful supplement to the bioinformatics pipelines, a wide range of cloud toolsets can further meet the needs of users for daily biological data processing, statistics, and visualization. The rich online courses of multi‐omics also provide a state‐of‐art platform to researchers in interactive communication and knowledge sharing.

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Six new steroidal saponins, solanigrosides C-H (2-7), and one known saponin, degalactotigonin (1), were isolated from the whole plant of Solanum nigrum. Their chemical structures were elucidated using spectroscopic analysis, chemical degradation, and derivatization. All seven compounds were tested for their cytotoxicity using four human tumor cell lines (HepG2, NCI-H460, MCF-7, SF-268). Only compound 1 was cytotoxic, with IC50 values of 0.25-4.49 microM.

Fusidane-type antibiotics represented by helvolic acid, fusidic acid and cephalosporin P1 are a class of bacteriostatic agents, which have drawn renewed attention because they have no cross-resistance to commonly used antibiotics. However, their biosynthesis is poorly understood. Here, we perform a stepwise introduction of the nine genes from the proposed gene cluster for helvolic acid into Aspergillus oryzae NSAR1, which enables us to isolate helvolic acid (~20 mg L−1) and its 21 derivatives. Anti-Staphylococcus aureus assay reveals that the antibacterial activity of three intermediates is even stronger than that of helvolic acid. Notably, we observe an unusual C-4 demethylation process mediated by a promiscuous short-chain dehydrogenase/reductase (HelC) and a cytochrome P450 enzyme (HelB1), which is distinct from the common sterol biosynthesis. These studies have set the stage for using biosynthetic approaches to expand chemical diversity of fusidane-type antibiotics.

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New diketopiperazines, epicoccins E-H (1-4) and diphenylalazines A (5) and B (6), have been isolated from the solid-substrate fermentation culture of the Cordyceps-colonizing fungus Epicoccum nigrum. The structures of 1-6 were determined primarily by NMR experiments, and the structure of 1 was confirmed by X-ray crystallography. The absolute configurations of 3 and 5 were assigned using the modified Mosher (3) and Marfey's (5) methods, respectively. Compounds 3-5 showed inhibitory effects on HIV-1 replication in C8166 cells. Diketopiperazines (DKPs) are an important class of compounds displaying a variety of biological effects, such as antimicorbial, herbicidal, antiviral, immunosuppressive, and antitumor activities. 1-3 Naturally occurring DKPs have frequently been isolated from fungal sources. Examples include golmaenone, a radical scavenger from a marine-derived Aspergillus sp., 4 the rostratins, cytotoxic DKP disulfides from a marine-derived Exserohilum rostratum, 5 the epicorazines, antibacterial metabolites from a basidiomycete Stereum hirsutum, 6 and the verticillins, dimeric DKPs from a marine-derived Penicillium sp. 7 Cordyceps sinensis (Berk.) Sacc. (Anamorph: Hirsutella sinensis; Clavicipataceae), 8 known as Chinese caterpillar fungus or "Dong Chong Xia Cao" (caterpillar-in-winter, herb-in-summer), is the combination of the fungus and the dead caterpillar larva of the moth Hepilus spp. It has been known and used for centuries in traditional Chinese medicine (TCM). 9 In nature, it is found only at high altitudes on the Himalayan Plateau and is therefore difficult to harvest. Chemical investigations of the fungal species that colonize the fruiting body of C. sinensis (Cordyceps-colonizing fungi) in our laboratory have led to the isolation of structurally diverse and biologically active metabolites. [10][11][12] In a search for anti-HIV-1 agents from this unique fungal source, the fungus Epicoccum nigrum (XZC04-CS-302) isolated from a sample of C. sinensis collected in Linzhi, Tibet, People's Republic of China, was grown in a solidsubstrate fermentation culture. Its organic solvent extract showed inhibitory effects on HIV-1 replication in C8166 cells. Fractionation of the extract afforded six new DKPs, named epicoccins E-H (1-4) and diphenylalazines A (5) and B (6), together with the known epicoccins A (7), B (8), and D (9), which were previously isolated by us from a different strain of Cordyceps-colonizing E. nigrum. 11 Details of the isolation, structure elucidation, and anti-HIV-1 activity of these metabolites are reported herein. Results and DiscussionEpicoccin E (1) was assigned the molecular formula C 18 H 18 N 2 O 7 S 2 (11 degrees of unsaturation) on the basis of its HRESIMS (m/z 461.0448 [M + Na] + ; ∆ +0.5 mmu). The 1 H and 13 C NMR data of 1 (Table 1) suggested the presence of three exchangeable protons (δ 5.56, 5.74, and 6.24, respectively), three methylenes, nine methines (five bonded to oxygen or nitrogen), two heteroatom-bonded sp 3 quaternary carbons, and four carbonyl carbons including ...