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Many microorganisms have mechanisms that protect cells against attack from viruses. The fermentation components of Streptomyces sp. 1647 exhibit potent anti-influenza A virus (IAV) activity. This strain was isolated from soil in southern China in the 1970s, but the chemical nature of its antiviral substance(s) has remained unknown until now. We used an integrated multi-omics strategy to identify the antiviral agents from this streptomycete. The antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) analysis of its genome sequence revealed 38 biosynthetic gene clusters (BGCs) for secondary metabolites, and the target BGCs possibly responsible for the production of antiviral components were narrowed down to three BGCs by bioactivity-guided comparative transcriptomics analysis. Through bioinformatics analysis and genetic manipulation of the regulators and a biosynthetic gene, cluster 36 was identified as the BGC responsible for the biosynthesis of the antiviral compounds. Bioactivity-based molecular networking analysis of mass spectrometric data from different recombinant strains illustrated that the antiviral compounds were a class of structural analogues. Finally, 18 pseudo-tetrapeptides with an internal ureido linkage, omicsynins A1–A6, B1–B6, and C1–C6, were identified and/or isolated from fermentation broth. Among them, 11 compounds (omicsynins A1, A2, A6, B1–B3, B5, B6, C1, C2, and C6) are new compounds. Omicsynins B1–B4 exhibited potent antiviral activity against IAV with the 50% inhibitory concentration (IC50) of approximately 1 µmol∙L–1 and a selectivity index (SI) ranging from 100 to 300. Omicsynins B1–B4 also showed significant antiviral activity against human coronavirus HCoV-229E. By integrating multi-omics data, we discovered a number of novel antiviral pseudo-tetrapeptides produced by Streptomyces sp. 1647, indicating that the secondary metabolites of microorganisms are a valuable source of novel antivirals.

Five Gram-stain-positive, aerobic, non-motile actinobacterial strains designated as CPCC 205763T, CPCC 203386T, CPCC 205716T, CPCC 203406T, and CPCC 203407 were obtained from different ecosystems associated with four kinds of Chinese traditional medicinal plants. The 16S rRNA gene sequences of these five strains showed closely related to members of the genus Herbiconiux of the family Microbacteriaceae, with the highest similarities of 97.4–99.7% to the four validly named species of Herbiconiux. In the phylogenetic trees based on 16S rRNA gene sequences and the core genome, these isolates clustered into the clade of the genus Herbiconiux within the lineage of the family Microbacteriaceae. The overall genome relatedness indexes (values of ANI and dDDH) and the phenotypic properties (morphological, physiological and chemotaxonomic characteristics) of these isolates, readily supported to affiliate them to the genus Herbiconiux, representing four novel species, with the isolates CPCC 203406T and CPCC 203407 being classified in the same species. For which the names Herbiconiux aconitum sp. nov. (type strain CPCC 205763T = I19A-01430T = CGMCC 1.60067T), Herbiconiux daphne sp. nov. (type strain CPCC 203386T = I10A-01569T = DSM 24546T = KCTC 19839T), Herbiconiux gentiana sp. nov. (type strain CPCC 205716T = I21A-01427T = CGMCC 1.60064T), and Herbiconiux oxytropis sp. nov. (type strain CPCC 203406T = I10A-02268T = DSM 24549T = KCTC 19840T) were proposed, respectively. In the genomes of these five strains, the putative encoding genes for amidase, endoglucanase, phosphatase, and superoxidative dismutase were retrieved, which were classified as biosynthetic genes/gene-clusters regarding plant growth-promotion (PGP) functions. The positive results from IAA-producing, cellulose-degrading and anti-oxidation experiments further approved their potential PGP bio-functions. Pangenome analysis of the genus Herbiconiux supported the polyphasic taxonomy results and confirmed their bio-function potential.

A Gram-stain-negative, rod-shaped, microcystin-degrading bacterium, designated as CPCC 100929T, was isolated from a fresh water reservoir in Sichuan Province, PR China. This isolate grew well at 4–37 °C and pH 6.0–8.0, with optimal growth at 28–32 °C and pH 7.0, respectively. The major cellular fatty acids were C18:1 ω7c/C18:1 ω6c, C16:0, C18:1 ω7c 11-methyl and C19:0 cyclo ω8c. The predominant respiratory quinone was Q-10. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and phosphatidylcholine were detected in the polar lipids extraction. The 16S rRNA gene sequence of strain CPCC 100929T was closely related to those of members of the genus Shinella , with the highest similarity of 98.6 % to Shinella zoogloeoides DSM 287T and 97.4–98.4 % with other identified Shinella members. In the phylogenetic trees based on 16S rRNA gene sequences and the core-genes analysis, strain CPCC 100929T was included within the clade of the genus Shinella . The values of average nucleotide identity (81.4–86.7 %) and digital DNA–DNA hybridization (25.4–44.6 %) between strain CPCC 100929T and other Shinella species were all below the thresholds for bacterial species delineation, respectively. The genomic DNA G+C content of strain CPCC 100929T was 63.6 %. The genomic sequence analysis indicated that this species contained genes encoding peroxidase, bla carbapenemase and the key enzyme for microcystin bio degradation, as well as rich carbohydrate-active enzyme coding genes, which might endow the micro-organism with properties to adapt to diverse environments. Based on its phenotypic and genetic properties, we propose that strain CPCC 100929T (=T1A350T=KCTC 72957T) is the type strain of a novel species with the name Shinella lacus sp. nov.

Diosgenin has been widely used as a precursor in the pharmaceutical industry. The conventional diosgenin production method, direct acid hydrolysis, can cause severe environmental pollution and has low production efficiency. In this study, the β-glucosidase FBG1 was successfully over-expressed in Pichia pastoris. The engineered yeast was grown in 5- and 50-L bioreactors to a high-cell-density, and the resulting recombinant FBG1 without purification was directly used for trillin biocatalysis. A novel enzymatic biocatalysis method was established through efficient biocatalysis of trillin by recombinant FBG1 and a practical diosgenin purification process. Diosgenin production reached ∼1.7 mg/mL under optimized biocatalysis conditions with a corresponding ∼94 % trillin conversion. The production process was further scaled up from 2 mL to 20, 200, and 2000 mL working volumes, producing equivalent efficiency. This recombinant enzyme biocatalysis process resulted in ∼680 mg diosgenin when 1 g trillin was processed, together with ∼90 % environmental impact elimination and ∼36 % cost reduction. Enzymatic biocatalysis can convert trillin into a high-value-added pharmaceutical precursor of diosgenin with high eco-efficiency, cost-effectiveness, and sustainability is presented here for the first time and is a promising method for future applications in industrial processes.

Members of the genus

Twenty-two metabolites were isolated from

The Antarctic and Arctic regions are collectively referred to as the “Two Poles” of the earth and have extremely harsh climate conditions and fragile ecosystems. Until now, the biogeography of the fungal communities in the bipolar regions is not well known. In this study, we focused on the fungal communities in 110 samples collected from four habitat types (i.e., soil, vascular plant, freshwater, moss) in the Antarctic and Arctic sites using high-throughput sequencing. The data showed that the diversity and composition of fungal communities were both geographically patterned and habitat-patterned. ANOSIM tests revealed statistically significant differences among fungal communities in the eight sample types (R = 0.5035, p < 0.001) and those in the bipolar regions (R = 0.32859, p < 0.001). Only 396 OTUs (14.8%) were shared between the bipolar sites. Fungal communities in the four habitat types clustered together in the Arctic site but were separate from those of the Antarctic site, indicating that geographic distance was a more important determinant of fungal communities in the bipolar sites. These findings offer insights into the present-day biogeography of fungal communities in the bipolar sites.

Three new phenolic metabolites, daldispols A–C (1–3), two new chromone derivatives, (5R,7R)-5,7-dihydroxy-2-methyl-5,6,7,8-tetrahydro-4H-chromen-4-one (9) and (5R,7R)-5,7-dihydroxy-2-propyl-5,6,7,8-tetrahydro-4H-chromen-4-one (10), together with five known phenolic compounds (4–8) and two known chromone compounds (11 and 12) were isolated from the endolichenic fungus Daldinia sp. CPCC 400770. Their structures were elucidated on the basis of spectroscopic methods, electronic circular dichroism (ECD), and comparison with reported data. Compounds 1, 3, 4, 9, and 11 exhibited significant anti-influenza A virus (IAV) activities with IC50 values of 12.7, 6.4, 12.5, 16.1, and 9.0 μM, respectively, and compound 8 displayed significant anti-ZIKV activity with inhibitory ratio of 42.7% at 10 μM. The results demonstrated that the fungus Daldinia sp. CPCC 400770 might be a rich source for discovering anti-IAV secondary metabolites as potential novel leading compounds.

Six new butyrolactone derivatives (1, 2a/2b, 3a/3b and 4), together with another two known derivatives (5 and 6) were isolated from the endophytic fungus Talaromyces sp. CPCC 400783. Their structures were established by a combination of spectroscopic analysis, including NMR and HRESIMS. The absolute configurations were elucidated by ECD experiments. Subsequently, compound 1, 3b, 4 and 5 exhibited good inhibitory effect against influenza A/WSN/33 (H1N1) virus with IC50 values of 21.93 ± 1.51, 21.54 ± 3.75, 18.36 ± 2.15 and 23.80 ± 3.05 μM respectively.

Four unusual cyclopeptides, zelkovamycins B-E (1-4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.

A Gram-stain-negative, aerobic, non-motile, pink-pigmented, coccus bacterium, designated CPCC 101081T, was isolated from a gravel soil sample collected from Badain Jara desert, PR China. Growth of the isolate occurred at 10–37 °C and pH 5.0–8.0, with optimal growth at 28–32 °C and pH 7.0, respectively. The major cellular fatty acids were summed feature 8 (C18:1ω7c/C18:1ω6c), summed feature 3 (C16:1ω6c/C16:1ω7c) and C18:12-OH. Q-10 was detected as the main respiratory quinone. Diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified phospholipid, an amino-containing lipid and an unidentified glycophospholipid were examined in the polar lipids extraction. The 16S rRNA gene sequence comparison of strain CPCC 101081Twith the available sequences in the GenBank database showed that the isolate was closely related to members of the genusRosenomonas, with the highest similarity toRoseomonas roseaDSM 14916T(97.4 %). In the phylogenetic trees based on 16S rRNA gene sequences and the core genomes, strain CPCC 101081Twas included within the clade of the genusRoseomonas, representing a species level, with the closest neighbor ofR. roseaDSM 14916T. The genomic DNA G+C content was 68.7 mol%. The average nucleotide identity and the digital DNA–DNA hybridization values between strain CPCC 101081Tand the related type strains of the genusRoseomonaswere all far lower than the cut-off values for definition species. On the basis of above phenotypic and genotypic characteristics, strain CPCC 101081Tis proposed to represent a novel species of the genusRoseomonaswith the nameRoseomonas harenaesp. nov. strain CPCC 101081T(=KCTC 62852T=NBRC 113512T) is the type strain of the species.

Particulate matter (PM) has been a threat to the environment and public health in the metropolises of developing industrial countries such as Beijing. The microorganisms associated with PM have an impact on human health if they are exposed to the respiratory tract persistently. There are few reports on the microbial resources collected from PM and their antimicrobial activities. In this study, we greatly expanded the diversity of available commensal organisms by collecting 1,258 bacterial and 456 fungal isolates from 63 PM samples. A total of 77 bacterial genera and 35 fungal genera were included in our pure cultures, with Bacillus as the most prevalent cultured bacterial genus, Aspergillus, and Penicillium as the most prevalent fungal ones. During heavy-haze days, the numbers of colony-forming units (CFUs) and isolates of bacteria and fungi were decreased. Bacillus, Paenibacillus, and Chaetomium were found to be enriched during haze days, while Kocuria, Microbacterium, and Penicillium were found to be enriched during non-haze days. Antimicrobial activity against common pathogens have been found in 40 bacterial representatives and 1 fungal representative. The collection of airborne strains will provide a basis to greatly increase our understanding of the relationship between bacteria and fungi associated with PM and human health.

Twenty-two metabolites were isolated from Penicillium sp. CPCC 401423 cultured on rice. The structures of all compounds were elucidated mainly by MS and NMR analysis as well as the necessary CD experimental evidence, of which penicillidione A (1), penicillidione B (2), (E)-4-[(4-acetoxy-3-methyl-2-butenyl)oxy]phenylacetic acid (3), (S)-2-hydroxy-2-{4-[(3-methyl-2-butenyl)oxy]phenyl} (4), (S)-4-(2,3-dihydroxy-3-methyl-butoxy)phenylacetic acid (5), (E)-4-[(3-carboxy-2-butenyl)oxy]benzoic acid (6), (Z)-4-[(4-hydroxy-3-methyl-2-butenyl)oxy]benzoic acid (7), open-cycled N-demethylmelearoride A (12), and penostatin M (16) were identified as new compounds. The cytotoxic activity against human pancreatic carcinoma cell line MIA PaCa-2a was detected. Among them, compounds 13–15 and 22 displayed significant cytotoxicity against MIA-PaCa-2 cells with IC50 values of 8.9, 36.5, 31.8, and 22.3 µM, respectively (positive control gemcitabine IC50 65.0 µM).

Fungi are widely distributed in all terrestrial ecosystems, and they are essential to the recycling of nutrients in all terrestrial habitats on earth. We wanted to determine the relationship between soil fungal communities and geochemical factors (geographical location and soil physicochemical properties) in three widely separated geographical regions (the Antarctic, Arctic, and Tibet Plateau). Using high-throughput Illumina amplicon sequencing, we characterized the fungal communities in 53 soil samples collected from the three regions. The fungal richness and diversity indices were not significantly different among the three regions. However, fungal community composition and many fungal taxa (Thelebolales, Verrucariales, Sordariales, Chaetothyriales, Hypocreales, Pleosporales, Capnodiales, and Dothideales) significantly differed among three regions. Furthermore, geographical location (latitude and altitude) and six soil physicochemical properties (SiO42−-Si, pH, NO3−-N, organic nitrogen, NO2−-N, and organic carbon) were significant geochemical factors those were correlated with the soil fungal community composition. These results suggest that many geochemical factors influence the distribution of the fungal species within the Antarctic, Arctic, and Tibet Plateau.

In this work, we isolated and characterized fusapyrone A (1), a new γ-pyrone derivative, along with six previously described compounds from the rice fermentation of Fusarium sp. CPCC 401218, a fung...

Polycyclic xanthones are secondary metabolites from actinomycetes and cervinomycin A and B are bioactive 26-membered polycyclic xanthones from Streptomyces sp. CPCC 204980. Herein, we report cervinomycins C1-4 (1–4) from the same strain. The structures of 1–4 were determined by 1D- and 2D-NMR, or single-crystal X-ray diffraction. Compounds 1–4 feature the open or loss of A (oxazolidine) ring in their angular polycyclic framework compared with cervinomycin B. Compounds 1–4 showed potent cytotoxicity against human cancer cell lines HCT116 and BxPC-3, with IC50 at 0.9–801.0 nM and strong anti-Gram-positive bacterial activity.

Strain CPCC 203383T, isolated from the surface-sterilized fruit of Cerasus pseudocerasus (Lindl.) G. Don, was taxonomically characterized based on a polyphasic investigation. It had the highest 16S rRNA gene sequence similarities with Ornithinimicrobium pekingense DSM 21552 (97.2 %) and O. kibberense DSM 17687T (97.2%). Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain formed a distinct phyletic branch within the genus Ornithinimicrobium and the whole genome sequence data analyses supported that strain CPCC 203383T was phylogenetically related to the Ornithinimicrobium species. The isolate shared a range of phenotypic patterns reported for members of the genus Ornithinimicrobium , but also had a range of cultural, physiological and biochemical characteristics that separated it from related Ornithinimicrobium species. The menaquinone was MK-8(H4). The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylinositol (PI) and unidentified lipids (ULs). The major fatty acids (>5 %) were iso-C15 : 0, anteiso-C15 : 0, iso-C16:0, 9-methyl C16 : 0, iso-C17 : 0 and anteiso-C17 : 0. The cell wall peptidoglycan contains l-ornithine as diagnostic diamino acid and an interpeptide bridge consisting of L-Orn←L-Ala←Gly←D-Asp. The combined genotypic and phenotypic data indicated that the isolate represents a novel species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium cerasi sp. nov. is proposed, with CPCC 203383T(=NBRC 113522T=KCTC 49200T) as the type strain. The DNA G+C composition is 72.3 mol%. The availability of new data allows for an emended description of the genus Ornithinimicrobium .

Lavanducyanin is a bioactive phenazine-containing secondary metabolite, and naphthomevalin is an antibacterial polyketide secondary metabolite. Herein, new analogues of lavanducyanin (2) and of naphthomevalin (4), together with lavanducyanin (1) and naphthomevalin (3), were identified from Streptomyces sp. CPCC 203577, an actinomycete soil isolate. The structures of 2 and 4 were elucidated as 1-hydroxy-7-oxolavanducyanin and Δ7″,8″-6″-hydroxynaphthomevalin, respectively, by 1D and 2D NMR. Antibacterial assays revealed that 2 had significant but reduced anti-Gram-positive bacterial activity compared with 1, and 4 was devoid of anti-Gram-positive bacterial activity. This indicated that the phenazinone nucleus in lavanducyanin and the monoterpene side chain in naphthomevalin might be important for their anti-Gram-positive bacterial activity. Compounds 1–4 were all inactive against Gram-negative bacteria.

A Gram-stain-negative, non-motile, coccobacillus-shaped bacterium, designated CPCC 101021T, was isolated from a sandy soil sample collected from Badain Jaran desert, China. Its 16S rRNA gene sequence was closely related to those of members of the genus Roseomonas, showing high similarities with Roseomonas hibiscisoli THG-N2.22T (98.0 %), Roseomonas oryzae KCTC 42542T (97.9 %), Roseomonas rhizosphaerae YW11T (97.9 %) and Roseomonas suffusca S1T (97.8 %). In the phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 101021T formed a distinct subclade with R. oryzae KCTC 42542T within the genus Roseomonas . Growth of the isolate occurred at 15–37 °C and pH 6.0–8.5, with optimal growth at 30 °C and pH 7.0. The major cellular fatty acids were C18 : 1ω7c, summed feature 8 (C16 : 1ω7c/C16 : 1ω6c), summed feature 3 (C16 : 1ω6c/C16 : 1ω7c) and C16 : 0ω6c. Q-10 was detected as the main component in the respiratory quinone system, with Q-9 as a minor component. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid and an unidentified glycolipid were found in the polar lipid profile. The genomic DNA G+C content was 68.7 mol%. The average nucleotide identity was 84.6 % when comparing the draft genome sequences of strain CPCC 101021T with R. oryzae KCTC 42542T. On the basis of genotypic, chemotaxonomic and phenotypic characteristics, strain CPCC 101021T is proposed to represent a novel species of the genus Roseomonas with the name Roseomonas vastitatis sp. nov. Strain CPCC 101021T (=J1A743T=KCTC 62043T) is the type strain of the species.

A novel actinobacterium, designated strain 16Sb5-5T, was isolated from a sand sample collected in the Taklamakan desert in Xinjiang Uygur Autonomous Region, China. The strain was examined by a polyphasic approach to clarify its taxonomic position. Cells of the isolate were Gram-staining-positive, aerobic, non-motile and short-rod shaped. Strain 16Sb5-5T grew optimally at 37 °C, pH 7.0 and with 0‒2 % (w/v) NaCl. The cell-wall peptidoglycan was of the A3γ type and contained alanine, glycine, glutamic acid and ll-diaminopimelic acid (ll-DAP). Ribose, arabinose and glucose were detected in the whole-cell hydrolysates. The predominant menaquinone was MK-9(H4). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified phospholipid, three unidentified glycolipids and three unidentified lipids. The major whole-cell fatty acids were anteiso-C15 : 0 and iso-C15 : 0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 16Sb5-5T was closely related to Desertihabitans aurantiacus CPCC 204711T (99.8 % similarity) and formed a robust clade with D. aurantiacus in the phylogenetic trees. In silico genomic comparisons showed that strain 16Sb5-5T exhibited ANI values of 94.8–94.9 % and GGDC value of 59.5 % to D. aurantiacus CPCC 204711T. The genomic G+C content was 73.3 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic analyses, strain 16Sb5-5T could be distinguishable from its closest phylogenetic relative and represents a novel species of the genus Desertihabitans , for which the name Desertihabitans brevis sp. nov. is proposed. The type strain is 16Sb5-5T (=KCTC 49116T=CGMCC 1.16553T). The description of the genus Desertihabitans has also been emended.

A Gram-stain-positive, aerobic bacterium, designated CPCC 204705T, was isolated from a desert soil sample, collected from the Badain Jaran desert. Growth of strain CPCC 204705T was observed at pH 6.0–8.0 and 15–37 °C, with optimal growth at 28 °C and pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204705T belonged to the genus Cellulomonas , showing the highest similarity (98.54 %) of 16S rRNA gene sequence to Cellulomonas oligotrophica JCM 17534T. The peptidoglycan type was A4β, containing d-ornithine and d-glutamic acids as diagnostic amino acids. Rhamnose and galactose were detected in the whole-cell hydrolysate as diagnostic sugars. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C15 : 1A, C14 : 0 and C16 : 0. The major menaquinone was MK-9 (H4) and the polar lipid system contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol mannoside, one unidentified lipid, one unidentified aminolipid and two unidentified aminophospholipids. The DNA–DNA hybridization value between strain CPCC 204705T and C. oligotrophica JCM 17534T was 7.1±0.4 %, and the value of average nucleotide identity between these two strains was 79.8 %. The DNA G+C content of strain CPCC 204705T was 75.4 mol%. Based on the results of physiological experiments, chemotaxonomic data, phylogenetic analysis and DNA–DNA hybridization value, strain CPCC 204705T should be classified as a novel Cellulomonas species. The name Cellulomonas telluris sp. nov. is proposed, with strain CPCC 204705T (=DSM 105430T=KCTC 39974T) as the type strain.

The recently discovered antibiotic burnettramic acid A (1) and three new congeners, burnettramic acids C–E (2–4), were identified from the co-cultures of two marine Aspergillus strains. The structure of burnettramic acid A was revised on the basis of reinterpretation of the nuclear magnetic resonance (NMR) data and chemical derivatization. The full absolute configurations of burnettramic acids were established using the Mosher ester method and Marfey’s analysis, combined with density functional theory calculation of NMR and electric circular dichroism data.

Three Gram-stain-positive, aerobic, motile actinobacterial strains designated as CPCC 205119T, CPCC 205215, and CPCC 205251 were isolated from different biological soil crust samples collected from Tengger Desert, China. The 16S rRNA gene sequence comparison of these three strains showed they had almost identical 16S rRNA genes, which were closely related to members of the family Geodermatophilaceae, with the highest similarities of 96.3–97.3% to the species of Modestobacter. In the phylogenetic tree based on 16S rRNA gene sequences, these isolates clustered into a subclade next to the branch containing the species of Modestobacter lapidis and Modestobacter multiseptatus, within the lineage of the genus Modestobacter. The comparative genomic characteristics (values of ANI, dDDH, AAI, and POCP) and the phenotypic properties (morphological, physiological, and chemotaxonomic characteristics) of these isolates readily supported to affiliate them to the genus Modestobacter as a single separate species. For which, we proposed that the isolates CPCC 205119T, CPCC 205215, and CPCC 205251 represent a novel species of the genus Modestobacter as Modestobacter deserti sp. nov. CPCC 205119T (=I12A-02624=NBRC 113528T=KCTC 49201T) is the type strain. The genome of strain CPCC 205119T consisted of one chromosome (4,843,235bp) containing 4,424 coding genes, 48 tRNA genes, five rRNA genes, three other ncRNA genes, and 101 pseudogenes, with G+C content of 74.7%. The whole-genome sequences analysis indicated that this species contained alkaline phosphatase genes (phoA/phoD), phosphate transport-related genes (phoU, phnC, phnD, phnE, phoB, phoH, phoP, phoR, pitH, ppk, pstA, pstB, pstC, and pstS), trehalose-phosphate synthase gene (otsA), trehalose 6-phosphate phosphatase gene (otsB) and other encoding genes for the properties that help the microorganisms to adapt to harsh environmental conditions prevalent in deserts. Strains of this species could solubilize tricalcium phosphate [Ca3(PO4)2] and phytin, assimilate pyrophosphate, thiophosphate, dithiophosphate, phosphoenol pyruvate, 2-deoxy-d-glucose-6-phosphate, and cysteamine-S-phosphate.

Three Gram-stain-positive, aerobic, motile actinobacterial strains designated as CPCC 205119T, CPCC 205215, and CPCC 205251 were isolated from different biological soil crust samples collected from Tengger Desert, China. The 16S rRNA gene sequence comparison of these three strains showed they had almost identical 16S rRNA genes, which were closely related to members of the family Geodermatophilaceae, with the highest similarities of 96.3–97.3% to the species of Modestobacter. In the phylogenetic tree based on 16S rRNA gene sequences, these isolates clustered into a subclade next to the branch containing the species of Modestobacter lapidis and Modestobacter multiseptatus, within the lineage of the genus Modestobacter. The comparative genomic characteristics (values of ANI, dDDH, AAI, and POCP) and the phenotypic properties (morphological, physiological, and chemotaxonomic characteristics) of these isolates readily supported to affiliate them to the genus Modestobacter as a single separate species. For which, we proposed that the isolates CPCC 205119T, CPCC 205215, and CPCC 205251 represent a novel species of the genus Modestobacter as Modestobacter deserti sp. nov. CPCC 205119T (=I12A-02624=NBRC 113528T=KCTC 49201T) is the type strain. The genome of strain CPCC 205119T consisted of one chromosome (4,843,235bp) containing 4,424 coding genes, 48 tRNA genes, five rRNA genes, three other ncRNA genes, and 101 pseudogenes, with G+C content of 74.7%. The whole-genome sequences analysis indicated that this species contained alkaline phosphatase genes (phoA/phoD), phosphate transport-related genes (phoU, phnC, phnD, phnE, phoB, phoH, phoP, phoR, pitH, ppk, pstA, pstB, pstC, and pstS), trehalose-phosphate synthase gene (otsA), trehalose 6-phosphate phosphatase gene (otsB) and other encoding genes for the properties that help the microorganisms to adapt to harsh environmental conditions prevalent in deserts. Strains of this species could solubilize tricalcium phosphate [Ca3(PO4)2] and phytin, assimilate pyrophosphate, thiophosphate, dithiophosphate, phosphoenol pyruvate, 2-deoxy-d-glucose-6-phosphate, and cysteamine-S-phosphate.

Background Resistance to anti-tuberculosis (TB) drugs is a major issue in TB control, and demands the discovery of new drugs targeting the virulence factor ESX-1. Methods We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacteria and reducing bacterial virulence. We further investigated the probability of inducing drug resistance and the underlying mechanism using mycobacterial protein fragment complementation. Results A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1–dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10–EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drugs, and exhibit high potency against chronic mycobacterial infection. Conclusions Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.

Biotransformation of the neo-clerodane diterpene, scutebarbatine F (1), by Streptomyces sp. CPCC 205437 was investigated for the first time, which led to the isolation of nine new metabolites, scutebarbatine F1–F9 (2–10). Their structures were determined by extensive high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR data analyses. The reactions that occurred included hydroxylation, acetylation, and deacetylation. Compounds 2–4 and 8–10 possess 18-OAc fragment, which were the first examples of 13-spiro neo-clerodanes with 18-OAc group. Compounds 7–10 were the first report of 13-spiro neo-clerodanes with 2-OH. Compounds 1–10 were biologically evaluated for the cytotoxic, antiviral, and antibacterial activities. Compounds 5, 7, and 9 exhibited cytotoxic activities against H460 cancer cell line with inhibitory ratios of 46.0, 42.2, and 51.1%, respectively, at 0.3 μM. Compound 5 displayed a significant anti-influenza A virus activity with inhibitory ratio of 54.8% at 20 μM, close to the positive control, ribavirin.

AntiSMASH analysis of genome DNA of Streptomyces CPCC 204980, a soil isolate with potent antibacterial activity, revealed a gene cluster for polycyclic xanthones. A subsequent chemical study confir...

Pichia pastoris is extensively used to produce various heterologous proteins. Amounts of biopharmaceutical drugs and industrial enzymes have been successfully produced by fed-batch high-cell-density fermentation (HCDF) of this cell factory. High levels of cell mass in defined media can be easily achieved and therefore large quantities of recombinant proteins with enhanced activities and lower costs can be obtained through HCDF technology. A robust HCDF process makes a successful transition to commercial production. Recently, efforts have been made to increase the heterologous protein production and activity by the HCDF of P. pastoris. However, challenges around selecting a suitable HCDF strategy exist. The high-level expression of a specific protein in P. pastoris is still, at least in part, limited by optimizing the methanol feeding strategy. Here, we review the progress in developments and applications of P. pastoris HCDF strategies for enhanced expression of recombinant proteins. We focus on the methanol induction strategies for efficient fed-batch HCDF in bioreactors, mainly focusing on various stat-induction strategies, co-feeding, and the limited induction strategy. These processes control strategies have opened the door for expressing foreign proteins in P. pastoris and are expected to enhance the production of recombinant proteins.

The taxonomic position of an actinobacterium, designated CPCC 204380T, which was isolated from a rhizosphere soil sample of the plant Calligonum mongolicum collected from Xinjiang Province, China, was established using a polyphasic approach. Vegetative hyphae developed well and globose bodies formed from aged hyphae. Spore chains that differentiated from the vegetative hyphae contained non-motile rod-shaped spores. The peptidoglycan contained meso-diaminopimelic acid and 3-hydroxydiaminopimelic acid as the diagnostic amino acids. The acyl type of the peptidoglycan was glycolyl. Glucose, mannose, ribose and xylose were detected in whole-cell hydrolysates. The predominant menaquinone was MK-10(H8), followed by MK-10(H6) and MK-10(H4). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were iso-C15 : 0, iso-C16 : 0 and C17 : 1ω9c. The genomic G+C content was 64.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204380T should be placed in the family Micromonosporaceae , in which it formed a distinct lineage next to the genera Rhizocola , Catellatospora , Catelliglobosispora , Hamadaea and Allocatelliglobosispora. It shared the highest 16S rRNA gene sequence similarities with Rhizocola hellebori K12-0602T (96.1 %), Catellatospora chokoriensis 2-25/1T (95.9 %), Catelliglobosispora koreensis DSM 44566T (95.9 %), Hamadaea tsunoensis DSM 44101T (95.3 %) and Allocatelliglobosispora scoriae Sco-B14 T (94.2 %), and less than 94.0 % sequence similarity with other validly described species. The combination of phylogenetic analysis and phenotypic characteristics supported the proposal of strain CPCC 204380T as representing a novel species of a new genus in the family Micromonosporaceae , for which the name Allorhizocola rhizosphaerae gen. nov., sp. nov. is proposed. CPCC 204380T (=DSM 102292T=KCTC 39746 T) is the type strain of the type species.

Geninthiocin is a thiopeptide with 35-membered macrocyclic core moiety. It has potent anti-Gram-positive (G+) bacteria activity. Herein, we reported two new congeners (2-3) of geninthiocin (geninthiocin A, 1) from Streptomyces sp. CPCC 200267, and designated them as geninthiocins C and D, whose structures were determined by NMR. Geninthiocins A, C and D had the same 35-membered macrocyclic core moiety, but possessed a -Dha-Dha-NH2, -Dha-Ala-NH2, and -NH2 tail, respectively. Besides, the Ala residue in geninthiocin C was determined as L- configuration by C3 Marfey's method. In vitro assays indicated that geninthiocins C-D showed no antibacterial activity, in contrast to the potent anti-G+ bacteria activity displayed by geninthiocin A. Therefore, the -Dha-Dha-NH2 tail of geninthiocin A played an important role in its potent activity against G+ bacteria.

A novel dark pink pigmented bacterium, designated strain CPCC 100847T (deposited with strain code 0113-15), was isolated from the urban air of Beijing, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CPCC 100847T was related to members of the genus Roseomonas and had the highest 16S rRNA gene sequence similarity to Roseomonas aestuarii JC17T (97.5 %). A low level of DNA–DNA relatedness (18.7 %) with its closest type strain R. aestuarii JC17T (KCTC 22692T) proved that strain CPCC 100847T belonged to a unique genomic species. CPCC 100847T had many common characteristics of the genus Roseomonas , but also had a range of cultural, physiological and biochemical characteristics that separated it from related Roseomonas species. Cells were Gram-negative, cocci- to oval-shaped, non-motile, non-endospore-forming and strictly aerobic. The respiratory ubiquinone was Q-10. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified aminolipid and an unidentified phospholipid. The major fatty acids (>5 %) were C18 : 1ω7c, anteiso-C15 : 0, C16 : 0, iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The combined genotypic and phenotypic data indicated that the isolate represents a novel species of the genus Roseomonas. The name proposed for this species is Roseomonas globiformis sp. nov., with CPCC 100847T (=KCTC 52094T) as the type strain. The DNA G+C composition is 65.2 mol%.

Diosgenin is used widely to synthesize steroidal hormone drugs in the pharmaceutical industry. The conventional diosgenin production process, direct acid hydrolysis of the root of Dioscorea zingiberensis C. H. Wright (DZW), causes large amounts of wastewater and severe environmental pollution. To develop a clean and effective method, the endophytic fungus Fusarium sp. CPCC 400226 was screened for the first time for the microbial biotransformation of DZW in submerged fermentation (SmF). Statistical design and response surface methodology (RSM) were implemented to develop the diosgenin production process using the Fusarium strains. The environmental variables that significantly affected diosgenin yield were determined by the two-level Plackett-Burman design (PBD) with nine factors. PBD indicates that the fermentation period, culture temperature, and antifoam reagent addition are the most influential variables. These three variables were further optimized using the response surface design (RSD). A quadratic model was then built by the central composite design (CCD) to study the impact of interaction and quadratic effect on diosgenin yield. The values of the coefficient of determination for the PBD and CCD models were all over 0.95. P-values for both models were 0.0024 and

Kongsfjorden in the high Arctic, a typical Arctic fjord, experienced long-time input of nutrients and pollutants from the remote and local resources, providing a platform for characterizing the diversity and distribution of antibiotic resistance genes (ARGs). However, the microbiome and antibiotic resistome in this pristine marine system have not been well documented. The present study aimed to identify the diversity and distribution of bacterial communities and associated ARGs in seawater (12 samples) and sediments (13 samples) of Kongsfjorden via metagenomic analysis. In terms of both bacterial community compositions and ARGs profiles, the seawater was significantly distinct from sediment. Only 29 ARG subtypes were detected in the Arctic seawater and sediments. Furthermore, three geochemical factors (i.e., longitude, depth, and PO43-) greatly influenced the bacterial communities in sediment samples, while longitude, depth, and latitude were crucial geochemical factors influencing the ARGs profiles in sediment samples. Procrustes analysis revealed a significant correlation between bacterial community compositions and ARG profiles in seawater and sediment samples. Network analysis further revealed the co-occurrence of metagenome-assembled genomes (MAGs) with ARG subtypes. Overall, our study provides insights into the microbiome and resistome in a pristine Arctic fjord, thereby providing vital information for environmental management.

In this work, we isolated and characterized fusapyrone A (

Three anthraquinone analogues (

Strain CPCC 203383

Three anthraquinone analogues (1–3) were isolated by phytochemical work on EtOAc-soluble ingredients extracted from the roots of Polygonatum odoratum. The structures of all isolates were elucidated by NMR, MS and CD experiments, of which 1 (polygodoquinone A) was identified as a new anthraquinone derivative. Specifically, 1 represents an unusual structure composed of a naphthoquinone derivative linked to an anthraquinone via a C-C bond. 1–3 exhibited remarkable influenza A virus inhibitory activity with IC50 values of 11.4, 11.0, and 2.3 μM, respectively, which were better than ribavirin as the positive control.

An intriguing structural feature of echinocandins is the incorporation of hydroxylated amino acids. Elucidation of the machinery and themechanism responsible for this modification is critical to generate new echinocandin derivativeswith enhanced antifungal activity. In our present study, we biochemically characterized the alpha-ketoglutarate/Fe2+-dependent proline hydroxylase (HtyE) from two Aspergillus species, Aspergillus pachycristatus and Aspergillus aculeatus, in the respective echinocandin B and aculeacin A biosynthetic gene clusters. Our results showed that both Ap-and Aa-HtyE converted L-proline to trans-4- and trans-3-hydroxyproline, but at different ratios. Both enzymes also effectively hydroxylated C-3 of 4R-methyl-proline, L-pipecolic acid, and D-proline. Our homology modeling and site-directed mutagenesis studies identified Leu182 of Ap-HtyE as a key residue in determining the regioselectivity of Ap-HtyE. Notably, we found that the efficiency in C-3 hydroxylation of 4R-methyl-proline has no direct correlation with the ratio of trans-4-hydroxylproline to trans-3-hydroxylproline catalyzed by HtyE. Deletion of Ap-htyE abolished A. pachycristatus anti-Candida activity and the production of echinocandin B, demonstrating that HtyE is the enzyme responsible for the hydroxylation of L-proline and 4R-methyl-proline in vivo and is essential for the anti-Candida activity of echinocandin B. Our present study thus sheds light on the biochemical basis for the selective hydroxylation of L-proline and 4R-methyl-proline and reveals a new type of biocatalyst with potential for the custom production of hydroxylated proline and pipecolic acid derivatives.

Baicalein, a dietary flavonoid, is the major constituent of Oroxylum indicum and Scutellaria baicalensis which are consumed as teas or dietary supplements in Asia, European, and the United States. The compound exhibits a variety of bioactivities despite its limited bioavailability. In the present work, 4-week treatment of baicalein significantly decreased the levels of blood glucose and circulating lipopolysaccharide (LPS) and improved insulin resistance, inflammation, and lipid profile in diabetic rats induced by STZ and high-fat-high-sugar-diet. These anti-diabetic effects were attributed to the increased SCFAs content and the increased thickness of gut mucus layer, and were associated with the modulation of gut microbiota. Among the key phylotypes, Bacteroides and Bacteroidales S24-7 had the highest relative abundance in the rats receiving high-dose baicalein and showed positive correlation with the phenotypes related to the improvement of type 2 diabetes (T2DM). Our study supports the use of baicalein as a dietary supplement and a potential prebiotic for its ability to modify gut microbiota and to improve T2DM-related biochemical abnormalities.

Glycosylation is an effective approach to improve the druggability of natural products by increasing their water solubility. In this work, we report the glycosylation of oleanane-type triterpenoids by a recombinant microbial glycosyltransferase YjiC1. A preliminary screening test indicated YjiC1 exhibited robust capabilities for O-glycosylation of triterpenoids, based on LC/MS analysis. Among the products, two new compounds (2a and 3a), together with a known one (1a), were isolated and characterized. These products exhibited improved water solubility, and 3a showed moderate anti-HIV activities at 100 μM. This reaction provides a facile and efficient approach to synthesize the glucosides of triterpenoids.

Three actinomycete strains originating from the surface-sterilized roots of Paris polyphylla were characterized by using a polyphasic approach. Phylogenetic analyses based on the 16S rRNA gene sequence showed that they formed a deep, monophyletic branch in the genus Glycomyces, and were most closely related to the type strains of the species Glycomyces harbinensis and Glycomycesscopariae. Morphological and chemotaxonomic data supported the affiliation of strains CPCC 204357T, CPCC 204354 and CPCC 204355 to the genus Glycomyces. The results of physiological and biochemical tests allowed phenotypic differentiation of strains CPCC 204357T, CPCC 204354 and CPCC 204355 from their closest phylogenetic related species in the genus Glycomyces. Low levels of DNA-DNA relatedness with its closest type strains of G. harbinensis and G. scopariaeindicated that strain CPCC 204357T represent a novel species, for which the name Glycomyces paridis sp. nov. is proposed, with CPCC 204357T (=DSM 102295T=KCTC 39745T) as the type strain.

Ahmpatinin iBu (1) and statinin iBu (2), two new linear peptides, a novel pyrrolidine derivative, (−)-(S)-2-[3-(6-methylheptanamido)-2-oxopyrrolidin-1-yl] acetic acid (3), and three known pepstatin derivatives (4–6) along with their corresponding methanolysis artifacts (7–9) were isolated from Streptomyces sp. CPCC 202950. Their structures were elucidated on the basis of extensive spectroscopic data using Marfey's analysis, chiral-phase HPLC, and ECD and OR calculation to determine the absolute configurations. Compound 1 contains an unusual amino acid, 4-amino-3-hydroxy-5-(4-methoxyphenyl)pentanoic acid (Ahmppa), and 3 is the first natural product with a 2-(3-amino-2-oxopyrrolidin-1-yl)acetic acid system. Compounds 1, 2, and 4–9 are HIV-1 protease inhibitors. In particular, ahmpatinin iBu (1) exhibits significant inhibitory activity against HIV-1 protease with an IC50 value of 1.79 nM. A preliminary structure–activity relationship is discussed.

Fungal communities play a significant role in regulating ecological processes in the Arctic tundra. However, the extent to which the Arctic moss species and host types (moss, lichen and vascular plant) determine the richness, diversity, and composition of fungal communities at a local scale has not been quantitatively explored. Using 454 pyrosequencing in the current study, we characterized the fungal communities associated with six moss species (Andreaea rupestris, Bryum pseudotriquetrum, Hymenoloma crispulum, Polytrichastrum alpinum, Racomitrium lanuginosum, and Sanionia uncinata) and compared them with fungal communities associated with lichens and vascular plants in the Ny-Alesund region (High Arctic). Host-species preference had greater explanatory power than geographical factors (longitude, latitude, elevation) in shaping moss-associated fungal communities. Fungal communities associated with mosses differed significantly from those associated with vascular plants and lichens, suggesting specificity of the fungal communities among three host types. Pairwise comparison analysis also indicated that the relative abundance of many taxonomic groups (e.g., Chaetothyriales, Leotiales, Catenulifera, Alatospora, and Toxicocladosporium) significantly differed between mosses and the other two host types. These results suggest host factors significantly affect the distribution of the fungal species associated with these moss species in the local-scale Arctic tundra.

Four new oxazole-containing diterpenoids, salvianans A–D (1–4), along with three known diterpenoids (5–7), were isolated from Salvia miltiorrhiza cell cultures. The structures of the new compounds were elucidated using spectroscopic methods and single-crystal X-ray diffraction. The evaluation for their anti-HIV-1 activities revealed that 2 and 3 displayed inhibitory activities with IC50 values of 0.03 and 1.2 μM, respectively. The time of addition (TOA) assay and long terminal repeat (LTR) luciferase reporter assay results indicated that compound 2 was an HIV-1 transcription inhibitor and might be a lead compound of antiviral agents acting on HIV-1 transcription.

A Gram-stain-positive, non-spore-forming actinobacterial strain, designated CPCC 204077T, was isolated from the surface-sterilized root of a medicinal plant Huperzia serrata (Thunb.) collected from Sichuan Province, south-west China. The peptidoglycan type of strain CPCC 204077T was detected as A4α with an l-Lys–l-Ser–d-Asp interpeptide bridge. Galactose, glucose, rhamnose and ribose were the sugar compositions in the whole-cell hydrolysates. MK-8(H4) was the only menaquinone. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, one unidentified phospholipid and one unidentified glycolipid. The major fatty acid was iso-C16 : 0. The genomic DNA G+C content was 71.0 mol%. The phylogenetic tree based on 16S rRNA gene sequences showed that strain CPCC 204077T stood for a distinct lineage within the family Dermacoccaceae alongside the genera Branchiibius , Demetria and Barrientosiimonas , with the highest 16S rRNA gene sequence similarities to Branchiibius hedensis Mer 29717T (95.0 %), Calidifontibacter indicus PC IW02T (95.0 %), Barrientosiimonas humi 39T (94.9 %) and Demetria terragena HKI 0089T (94.7 %), and less than 94.7 % sequence similarities to all other species. Signature nucleotides in the 16S rRNA sequence showed that the strain contained the Dermacoccaceae family-specific 16S rRNA signature nucleotides and a genus-specific diagnostic nucleotide signature pattern. Combining the genotypic and phenotypic analyses, we propose that strain CPCC 204077T represents a novel species of a new genus in the family Dermacoccaceae with the name Allobranchiibius huperziae gen. nov., sp. nov. Strain CPCC 204077T (=NBRC 110719T=DSM 29531T) is the type strain of the type species.

Twenty-three new C21 steroidal glycosides, marstenacissides C1–C10 (1–10), D1–D7 (11–17) and E1–E6 (18–23), and four new C21 steroids, 11α,12β-O-ditigloyl-tenacigenin C (24), 11α-O-benzoyl-12β-O-tigloyl-tenacigenin C (25), 11α-O-tigloyl-12β-O-benzoyl-tenacigenin C (26) and 11α-O-tigloyl-12β-O-benzoyl-marsdenin (27), were isolated from the Dai herbal medicine Dai-Bai-Jie, derived from the roots of Marsdenia tenacissima. The chemical structures of all compounds were established by spectroscopic techniques, including high-resolution mass spectrometry and NMR spectroscopy, as well as by comparison with reported spectral data. The anti-HIV activities of these compounds were screened, and the compounds obtained displayed inhibitory effects against HIV-1 with inhibition rates of 36.4–81.3% at 30 μM.

Protein kinase B (PknB) is one of the Mycobacterium tuberculosis serine/threonine protein kinases and has an essential role in sustaining mycobacterial growth. Here, we identified and characterized a novel small molecule compound named IMB-YH-8 that inhibited PknB and served as anti-mycobacteria lead compound. IMB-YH-8 inhibited PknB auto-phosphorylation and the phosphorylation of GarA by PknB in a dose-dependent manner. The compound did not inhibit human Akt1 or other serine/threonine kinases in M. tuberculosis except for the highly homologous PknA. IMB-YH-8 bound to PknB with a moderate affinity. Molecular docking revealed that IMB-YH-8 interacts with the catalytic domain of PknB. Observations of electron microscopy showed that IMB-YH-8 changed the morphology of H37Rv and disrupted the cell wall. The differential transcriptional response of M. tuberculosis to IMB-YH-8 revealed changes in SigH regulatory pathways modulated by PknB. Notably IMB-YH-8 not only potently inhibited drug-sensitive and multidrug-resistant clinical isolates but also exhibited a dose dependent inhibition of intracellular M. tuberculosis. Taken together, these in vitro data demonstrate that IMB-YH-8 is a novel inhibitor of PknB, which potently prevents growth of M. tuberculosis. It is as yet unclear whether inhibition of PknA contributes to the anti-tubercular action of IMB-YH-8.

Four new farnesylated isoindolinone derivatives, named stachybotrysams A–D ( 2 – 5 ), and one new farnesyl-cyclized analogue, named stachybotrysam E ( 6 ), as well as one known congener ( 1 ), were isolated from the filamentous fungus Stachybotrys chartarum CGMCC 3.5365. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and by comparison with reported data. Compounds 2–4 exhibited significant HIV-inhibitory activity with IC 50 values of 9.3, 1.0, and 9.6 μ M, respectively.