Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

Unique Cyclized Thiolopyrrolones from the Marine-Derived Streptomyces sp. BTBU20218885.

Two new cyclized thiolopyrrolone derivatives, namely, thiolopyrrolone A (1) and 2,2-dioxidothiolutin (2), together with the kn own compound, thiolutin (3) were identified from a marine-derived Streptomyces sp. BTBU20218885, which was isolated from a mud sample collected from the coastal region of Xiamen, China. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D and 2D NMR techniques. 1 possessed a unique unsymmetrical sulfur-containing thiolopyrrolone structure. All the compounds were tested for bioactivities against Staphylococcus aureus, Escherichia coli, Bacille Calmette-Guérin (BCG), Mycobacterium tuberculosis, and Candida albicans. 1 displayed antibacterial activities against BCG, M. tuberculosis, and S. aureus with minimum inhibitory concentration (MIC) values of 10, 10, and 100 µg/mL, respectively. Thiolutin (3) showed antibacterial activities against E. coli, BCG, M. tuberculosis, and S. aureus with MIC values of 6.25, 0.3125, 0.625, and 3.125 µg/mL, respectively.

Chaetoglobosins and azaphilones from Chaetomium globosum associated with Apostichopus japonicus.

Increasing attention has recently been focused on complex symbiotic associations, for instance coral and its symbionts. Sea cucumber, harboring diverse fungi, has also attracted more and more attention for their functional diversity. Here, secondary metabolites produced by Chaetomium globosum associated with sea cucumber, Apostichopus japonicus, were investigated using gene mining with third-generation sequencing technology (PacBio SMRT). Nine compounds, including one new compound cytoglobosin X (1), were isolated from cultures of Chaetomium globosum. Compound 1 was identified based on NMR data, HRESIMS, and ECD, and the absolute configurations were identified as 3S, 4R, 7S, 8R, 9R, 16S, 19S, 20S, and 23S. In an antimicrobial assay, compound 4 showed moderate activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with MICs of 47.3 and 94.6 µM, respectively. Our results suggest that the microbiomes associated with sea cucumber could be an important resource for biodiversity and structural novelty, and the bioactive compounds may protect the host from pathogen microbial.

Genome- and MS-based mining of antibacterial chlorinated chromones and xanthones from the phytopathogenic fungus Bipolaris sorokiniana strain 11134.

Halogen substituents are important for biological activity in many compounds. Genome-based mining of halogenase along with its biosynthetic gene cluster provided an efficient approach for the discovery of naturally occurring organohalogen compounds. Analysis of the genome sequence of a phytopathogenic fungus Bipolaris sorokiniana 11134 revealed a polyketide gene cluster adjacent to a flavin-dependent halogenase capable of encoding halogenated polyketides, which are rarely reported in phytopathogenic fungi. Furthermore, MS- and UV-guided isolation and purification led to the identification of five chlorine-containing natural products together with seven other chromones and xanthones. Two of the chlorinated compounds and four chromones are new compounds. Their structures were elucidated by NMR spectroscopic analysis and HRESIMS data. The biosynthetic gene clusters of isolated compounds and their putative biosynthetic pathway are also proposed. One new chlorinated compound showed activity against Staphylococcus aureus, methicillin-resistant S. aureus, and three clinical-resistant S. aureus strains with a shared minimum inhibitory concentration (MIC) of 12.5 µg/mL. Genome-based mining of halogenases combined with high-resolution MS- and UV-guided identification provides an efficient approach to discover new halogenated natural products from microorganisms.

New Diketopiperazines from a Marine-Derived Fungus Strain Aspergillus versicolor MF180151.

Six new diketopiperazines, (±)-7,8-epoxy-brevianamide Q ((±)-1), (±)-8-hydroxy-brevianamide R ((±)-2), and (±)-8-epihydroxy-brevianamide R ((±)-3), together with four known compounds, (±)-brevianamide R ((±)-4), versicolorin B (5) and averufin (6), were isolated from a marine-derived fungus strain Aspergillus versicolor MF180151, which was recovered from a sediment sample collected from the Bohai Sea, China. The chemical structures were established by 1D- and 2D-NMR spectra and HR-ESI-MS. 1 is the first sample of brevianamides with an epoxy moiety. Their bioactivities were evaluated against Candida albicans, Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Bacillus Calmette-Guérin. Compounds 1-4 showed no activities against the pathogens, and compounds 5 and 6 showed moderate activities against S. aureus and methicillin-resistant S. aureus.

Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction.

During cell renewal, epigenetic information needs to be precisely restored to maintain cell identity and genome integrity following DNA replication. The histone mark H3K27me3 is essential for the formation of facultative heterochromatin and the repression of developmental genes in embryonic stem cells. However, how the restoration of H3K27me3 is precisely achieved following DNA replication is still poorly understood. Here we employ ChOR-seq (Chromatin Occupancy after Replication) to monitor the dynamic re-establishment of H3K27me3 on nascent DNA during DNA replication. We find that the restoration rate of H3K27me3 is highly correlated with dense chromatin states. In addition, we reveal that the linker histone H1 facilitates the rapid post-replication restoration of H3K27me3 on repressed genes and the restoration rate of H3K27me3 on nascent DNA is greatly compromised after partial depletion of H1. Finally, our in vitro biochemical experiments demonstrate that H1 facilitates the propagation of H3K27me3 by PRC2 through compacting chromatin. Collectively, our results indicate that H1-mediated chromatin compaction facilitates the propagation and restoration of H3K27me3 after DNA replication.

Antitubercular metabolites from the marine-derived fungus strain Aspergillus fumigatus MF029.

During the systematic screening of bioactive compounds from our marine natural product library, crude extract of the marine-derived fungus strain Aspergillus fumigatus MF029 exhibited moderate bioactivities against Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus, and Mycobacterium bovis bacillus Calmette-Guérin (BCG). Further chemical investigation resulted in the identification of two new compounds, chaetominine A (1) and sphingofungin I (2), together with four known compounds, emodin (3), chaetominine (4), sphingofungin D (5) and trypacidin (6). Trypacidin displayed potential antitubercular activity with MIC value of 1.25 µg/mL.

One new xanthenone from the marine-derived fungus Aspergillus versicolor MF160003.

A new xanthenone derivative, 3-hydroxy pinselin (1), together with five known analogues (2-6) were isolated from the marine-derived fungus Aspergillus versicolor MF160003. Their structures were identified by extensive 1D- and 2D-NMR, and high-resolution mass spectrometry data. Compounds 5 and 6 showed moderate bioactivities against BCG with MIC values of 40 and 20 µg/mL, respectively.

Use of the lichen Xanthoria mandschurica in monitoring atmospheric elemental deposition in the Taihang Mountains, Hebei, China.

Air pollution is a major concern in China. Lichens are a useful biomonitor for atmospheric elemental deposition but have rarely been used in North China. The aim of this study was to investigate the atmospheric depositions of 30 trace elements (Al, Ba, Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, K, La, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, Sb, Sc, Sm, Sr, Tb, Th, Ti, Tl, V and Zn) in a region of the Taihang Mountains, Hebei Province, China using lichens as biomonitors. Epilithic foliose lichen Xanthoria mandschurica was sampled from 21 sites and analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The results show that 1) eight elements (Cd, Cr, Cu, Mo, P, Pb, Sb and Zn) are of atmospheric origin and are highly influenced by the atmospheric transportation from the North China Plain, as well as local mining activities, while 2) the remaining 22 elements are primarily of crustal origin, the concentration of which has been enhanced by local mining and quarrying activities. These results clearly validate the applicability of lichens in biomonitoring of atmospheric elemental deposition and demonstrate the spatial pattern for air pollution in the region.

Lichen elemental composition distinguishes anthropogenic emissions from dust storm inputs and differs among species: Evidence from Xilinhot, Inner Mongolia, China.

To test the applicability of lichens in the biomonitoring of atmospheric elemental deposition in a typical steppe zone of Inner Mongolia, China, six foliose lichens (Physcia aipolia, PA; P. tribacia, PT; Xanthoria elegans, XE; X. mandschurica, XM; Xanthoparmelia camtschadalis, XPC; and Xp. tinctina, XPT) were sampled from the Xilin River Basin, Xilinhot, Inner Mongolia, China. Twenty-five elements (Al, Ba, Cd, Ce, Cr, Cs, Cu, Fe, K, La, Mn, Mo, Na, Ni, P, Pb, Sb, Sc, Sm, Tb, Th, Ti, Tl, V and Zn) in the lichens were analysed using inductively coupled plasma mass spectrometry (ICP-MS). The results show that Cd, Pb and Zn were mainly atmospheric in origin, whereas the other elements were predominantly of crustal origin. Compared with other studies, our data were higher in crustal element concentrations and lower in atmospheric element concentrations, matching with the frequent, severe dust storms and road traffic in the area. The elemental concentrations in lichens are both species- and element-specific, highlighting the importance of species selection for biomonitoring air pollution using lichens. We recommend PT, XE, XM and XPT for monitoring atmospheric deposition of crustal elements; XPC and XPT for Cd and Pb; PA for Cd and Zn; and PT for Cd.