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In the 1990s and 2000s, the enzymes macrophomate synthase, lovastatin polyketide synthase, solanapyrone synthase and riboflavin synthase were identified and proven to catalyse cyclohexene ring formation. Shortly after, Lei I et al. i identified the flavin adenine dinucleotide-dependent enzyme MaDA that can catalyse an intermolecular DA reaction to produce the isoprenylated flavonoid chalcomoracin in plant [[6]] (Fig. The Diels-Alder (DA) reaction is a simple yet very powerful pericyclic transformation involving the cycloaddition of a 1,3-diene and a dienophile to synthesize a cyclohexene ring via a cyclic transition state. [Extracted from the article]

PKSEbiosynthesizes an enediyne core precursor from decarboxylativecondensation of eight malonyl-CoAs. The KR domain of PKSE is responsiblefor iterative β-ketoreduction in each round of polyketide chainelongation. KRs from selected PKSEs were investigated in vitro withβ-ketoacyl-SNACs as substrate mimics. Each of the KRs reducedthe β-ketoacyl-SNACs stereoselectively, all affording the correspondingβ-d-hydroxyacyl-SNACs, and the catalytic efficiencies(kcat/KM)of the KRs increased significantly as the chain length of the β-ketoacyl-SNACsubstrate increases. [ABSTRACT FROM AUTHOR]

Four new tetrahydrochromanone derivatives, cochliones A-D (1-4), along with three known metabolites, 4-hydroxybenzaldehyde (5), 4-hydroxy-3-(3-methylbut-2-enyl) benzoic acid (6), and 2,2-dimethyl-2H-chromene-6-carboxylic acid (7), were characterized from the culture of Cochliobolus sp. IFB-E039, a fungus that resides inside the healthy root of Cynodon dactylon (Gramineae). The structures of 1-4 were accommodated by their spectral data (UV, IR, CD, HR-ESI-MS, 1H and 13C NMR, 1H-1H COSY, HMQC, HMBC, and NOESY). The bioassay for the cytotoxic metabolite showed that cochlione C (3) inhibited human breast adenocarcinoma cell line (MCF-7) and human chronic myeloid leukemia cell line (K562) with IC50 values of 21.99 and 4.59 μg/ml, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Along with the known secondary metabolites lumichrome, physcion, and emodin-1,6-dimethyl ether, three alkaloids named penicidones A–C (1–3) were isolated from the culture of Penicillium sp. IFB-E022, an endophytic fungal strain residing in the stem of Quercus variabilis (Fagaceae). The structures of penicidones A–C were established by a correlative interpretation of spectroscopic data including IR, UV and HR-ESI-MS, as well as by analysis of a set of 1D and 2D NMR experiments. The stereochemistry of compounds 1 and 2 was obtained by comparison of the optical rotation with those of vermistatin and its analogues. Penicidones A–C were the first group of natural products possessing a penicidone framework. Compounds 1–3 exhibited moderate cytotoxicity against four cancer cell lines. [Copyright &y& Elsevier]

Abstract: A series of Schiff bases (compounds 1–26) were synthesized by reacting 5-chloro-salicylaldehyde and primary amines, 15 (compounds 2–4, 6, 7, 10, 12–17, 23, 25 and 26) of which were first reported. The chemical structures of these compounds were confirmed by means of 1H NMR, 13C NMR, ESI-MS and elemental analyses. The compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the compounds tested, (E)-4-chloro-2-((4-fluorobenzylimino)methyl)phenol (2) showed the most favorable antimicrobial activity with MICs of 45.2, 1.6, 2.8, 3.4, and 47.5μg/mL against B. subtilis, E. coli, P. fluorescence, S. aureus and A. niger, respectively. [Copyright &y& Elsevier]

Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine‐tuned rigid three‐dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C−C and C−O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post‐translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450‐modified multicyclic RiPPs, we set out to find cryptic and unknown P450‐modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450‐modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450‐modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450‐modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring‐forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane‐containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives. [ABSTRACT FROM AUTHOR]

Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine‐tuned rigid three‐dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C−C and C−O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post‐translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450‐modified multicyclic RiPPs, we set out to find cryptic and unknown P450‐modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450‐modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450‐modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450‐modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring‐forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane‐containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives. [ABSTRACT FROM AUTHOR]

Precursor-fed cultivation of endophytic Chaetomium globosum1C51 afforded nine novel “unnatural” halogenated chaetoglobosins including those with more preferable immunosuppressive activity. [ABSTRACT FROM AUTHOR]

Phomactin diterpenoids possess a unique bicyclo[9.3.1]pentadecane skeleton with multiple oxidative modifications, and are good platelet‐activating factor (PAF) antagonists that can inhibit PAF‐induced platelet aggregation. In this study, we identified the gene cluster (phm) responsible for the biosynthesis of phomactins from a marine fungus, Phoma sp. ATCC 74077. Despite the complexity of their structures, phomactin biosynthesis only requires two enzymes: a type I diterpene cyclase PhmA and a P450 monooxygenase PhmC. PhmA was found to catalyze the formation of the phomactatriene, while PhmC sequentially catalyzes the oxidation of multiple sites, leading to the generation of structurally diverse phomactins. The rearrangement mechanism of the diterpene scaffold was investigated through isotope labeling experiments. Additionally, we obtained the crystal complex of PhmA with its substrate analogue FGGPP and elucidated the novel metal‐ion‐binding mode and enzymatic mechanism of PhmA through site‐directed mutagenesis. This study provides the first insight into the biosynthesis of phomactins, laying the foundation for the efficient production of phomactin natural products using synthetic biology approaches. [ABSTRACT FROM AUTHOR]

Phomactin diterpenoids possess a unique bicyclo[9.3.1]pentadecane skeleton with multiple oxidative modifications, and are good platelet‐activating factor (PAF) antagonists that can inhibit PAF‐induced platelet aggregation. In this study, we identified the gene cluster (phm) responsible for the biosynthesis of phomactins from a marine fungus, Phoma sp. ATCC 74077. Despite the complexity of their structures, phomactin biosynthesis only requires two enzymes: a type I diterpene cyclase PhmA and a P450 monooxygenase PhmC. PhmA was found to catalyze the formation of the phomactatriene, while PhmC sequentially catalyzes the oxidation of multiple sites, leading to the generation of structurally diverse phomactins. The rearrangement mechanism of the diterpene scaffold was investigated through isotope labeling experiments. Additionally, we obtained the crystal complex of PhmA with its substrate analogue FGGPP and elucidated the novel metal‐ion‐binding mode and enzymatic mechanism of PhmA through site‐directed mutagenesis. This study provides the first insight into the biosynthesis of phomactins, laying the foundation for the efficient production of phomactin natural products using synthetic biology approaches. [ABSTRACT FROM AUTHOR]

The objectives of this study were (1) to investigate the effect of extracts from some plants in the families Nelumbonaceae and Nymphaeaceae on phosphodiesterase 5 (PDE5) and arginase, which have been used in erectile dysfunction treatment, and (2) to isolate and identify the compounds responsible for such activities. The characterization and quantitative analysis of flavonoid constituents in the active extracts were performed by HPLC. Thirty-seven ethanolic extracts from different parts of plants in the genus Nymphaea and Victoria of Nymphaeaceae and genus Nelumbo of Nelumbonaceae were screened for PDE5 and arginase inhibitory activities. The ethanolic extracts of the receptacles and pollens of Nelumbo nucifera Gaertn., petals of Nymphaea cyanea Roxb. ex G.Don, Nymphaea stellata Willd., and Victoria amazonica (Poepp.) Sowerby and the petals and receptacles of Nymphaea pubescens Willd. showed IC50 values on PDE5 of less than 25 μg/mL while none of the extracts showed effects on arginase. The most active extract, N. pubescens petal extract, was fractionated to isolate and identify the PDE5 inhibitors. The results showed that six flavonoid constituents including quercetin 3'-O-β-xylopyranoside (1), quercetin 3-methyl ether 3'-O-β-xylopyranoside (2), quercetin (3), 3-O-methylquercetin (4), kaempferol (5) and 3-O-methylkaempferol (6) inhibited PDE5 with IC50 values at the micromolar level. [ABSTRACT FROM AUTHOR]

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs. [ABSTRACT FROM AUTHOR]

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs. [ABSTRACT FROM AUTHOR]

Lorneic acid and related natural products are characterized by a trialkyl‐substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl‐substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450‐catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450. [ABSTRACT FROM AUTHOR]

Lorneic acid and related natural products are characterized by a trialkyl‐substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl‐substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450‐catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450. [ABSTRACT FROM AUTHOR]

Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C−C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels–Alderase SdnG catalyzes an intramolecular Diels–Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton. [ABSTRACT FROM AUTHOR]

Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C−C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels–Alderase SdnG catalyzes an intramolecular Diels–Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton. [ABSTRACT FROM AUTHOR]

Leinamycin (LNM, 1 ) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2 ) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4′-dideshydroxy-LNM ( 5 ) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1 ; 5 exhibits comparable activity as 1 with the EC 50 values between 8.21 and 275 nM. This work reveals new insight into the structure–activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery. [ABSTRACT FROM AUTHOR]

Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13C‐labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin‐dependent monooxygenase ChaZ catalyses a Baeyer–Villiger oxidation on resomycin C to form a seven‐membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and affords the α‐pyrone containing pentacyclic intermediate in an NADPH‐dependent manner via tandem reactions including the reduction of the lactone carbonyl group, Aldol‐type reaction, followed by a spontaneous γ‐lactone ring formation, oxidation and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide. [ABSTRACT FROM AUTHOR]

Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13C‐labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin‐dependent monooxygenase ChaZ catalyses a Baeyer–Villiger oxidation on resomycin C to form a seven‐membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and affords the α‐pyrone containing pentacyclic intermediate in an NADPH‐dependent manner via tandem reactions including the reduction of the lactone carbonyl group, Aldol‐type reaction, followed by a spontaneous γ‐lactone ring formation, oxidation and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide. [ABSTRACT FROM AUTHOR]

Abstract: On the basis of analyzing the shortages of present studies on multi-echelon inventory control, and considering some restrictions, this paper applies the joint replenishment strategy into the inventory system and builds a multi-product multi-echelon inventory control model. Then, an algorithm designed by Genetic Algorithm (GA) is used for solving the model. Finally, we respectively simulate the model under three different ordering strategies. The simulation result shows that the established model and the algorithm designed by GA have obvious superiority on reducing the total cost of the multi-product multi-echelon inventory system. Moreover, it illustrates the feasibility and the effectiveness of the model and the GA method. [Copyright &y& Elsevier]

In this study, we evaluated the effects of hopeahainol A, a novel acetylcholinesterase inhibitor (AChEI) from Hopea hainanensis, on H2O2-induced cytotoxicity in PC12 cells and the possible mechanism. Exposure of PC12 cells to 200μM H2O2 caused cell apoptosis, reduction in cell viability and antioxidant enzyme activities, increment in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH). Pretreatment of the cells with hopeahainol A at 0.1–10μM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. Moreover, hopeahainol A could mitigate intracellular accumulation of reactive oxygen species (ROS) and Ca2+, the loss of mitochondrial membrane potential (MMP), and the increase of caspase-3, -8 and -9 activities induced by H2O2. These results show that hopeahainol A protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS and prevention of apoptosis. There was potential for hopeahainol A to be used in treating Alzheimer''s disease (AD) that involved acetylcholinesterase, free radical, oxidative damage and cell apoptosis. [Copyright &y& Elsevier]

• Murayaquinones B-E (1 – 4) were isolated from an insect derived actinobacterium. • Structures of new compounds were elucidated by analysis their spectroscopic data. • Murayaquinone D exhibited cytotoxic activities against six cancer cell lines. Chemical study of the insect-derived bacterium, Streptomyces sp. NA4286, led to the discovery of four new polyketides, murayaquinones B-E (1 – 4), together with a known compound, murayaquinone (5). The structures of new compounds (1 – 4) were determined by extensive analysis of their NMR and HRESIMS data. The absolute configuration of (+)- 1 and (−)- 1 was assigned through comparison of experimental and calculated ECD spectra. Murayaquinone D (3) exhibited potent cytotoxic activities against six human cancer cell lines with IC 50 values ranging from 1.03 to 9.99 μM. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New borrelidin-type macrolactones were isolated from an endophyte. • The structures of new compounds were elucidated by spectroscopic data. • Borrelidin A showed potent activity against M. luteus with MIC value of 1.0 μM. Abstract Three new borrelidin-type macrolactones, designated as borrelidins J−L (4 – 6), together with borrelidin A (1), borrelidin E (2), and 12-desnitrile-12-carboxyl-borrelidin (3) were isolated from a plant endophytic Streptomyces sp. NA06554. Their structures were determined by extensive spectroscopic analysis including HRESIMS, 1D and 2D NMR data. The antibacterial activities for compounds 1 – 6 were examined. Borrelidins A (1) and L (6) showed potent and moderate antibacterial activity against Micrococcus luteus , respectively, whereas other derivatives (2 – 5) are almost inactive, which allows us to propose a plausible structure-activity relationship. [ABSTRACT FROM AUTHOR]

Abstract: Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse‐transcription PCR (RT‐PCR) enabled two strains to produce eight new and two known meroterpenoids (1–10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide‐terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4‐dihydroxy‐6‐alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1–10. [ABSTRACT FROM AUTHOR]

Abstract: Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse‐transcription PCR (RT‐PCR) enabled two strains to produce eight new and two known meroterpenoids (1–10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide‐terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4‐dihydroxy‐6‐alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1–10. [ABSTRACT FROM AUTHOR]

Chaetospirolactone (1), a novel spiro-lactone bearing a rare 1-oxaspiro [4.4] non-7-ene-2,6-dione skeleton, and orsellide F (2), together with six known compounds (3-8), were isolated from an endophytic fungus Chaetomium sp. NF00754. Their structures were determined by interpretation of spectroscopic data. The absolute configurations of 1 and 2 were established by analysis of single X-ray crystallographic data and CD spectra. Compounds 3, 4, and 6 showed moderate acetylcholinesterase inhibitory activity with IC50 values of 7.34, 5.19, and 7.67 μM, respectively. [ABSTRACT FROM AUTHOR]

Five new aromatic polyketides, alternaphenols A–E ( 1 – 5 ), and two known compounds ( 6 – 7 ) were isolated from a liquid culture of Alternaria sp. (strain no. NF2198), a caterpillar associated fungus. Their structures were determined by extensive spectroscopic analysis and single crystal X-ray crystallography. Compounds 1 – 7 were evaluated for their cytotoxic activities against a human skin melanoma A-375 cell line. Only compounds 4 and 5 showed weak cytotoxic activities. [ABSTRACT FROM AUTHOR]

[Display omitted] Salinopyridins A and B, two novel polyethers containing a rare pyridine moiety, were isolated from an earwig symbiotic Streptomyces sp. NA4227. Their structures were determined by extensive spectroscopic analysis. Based on the structure, bioinformatics analysis and gene mutation experiments, we proposed that salinopyridins share the same biosynthetic pathway with salinomycin, and the formation of pyridine moiety is assembled through a nonenzymatic process. Salinopyridins A and B exhibited potent activity against several Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Seven new compounds, pleosporallins A–G ( 1 – 7 ), were isolated from Pleosporales sp., a fungus derived from a marine alga Enteromorpha clathrata . The structures of these compounds were elucidated by an extensive analysis of NMR, MS, CD spectra, and single crystal X-ray diffraction. Compounds 4 and 5 showed antimicrobial activity with their MIC values of 9.48 μg/ml and 7.44 μg/ml against Clavibacter michiganense subsp. Sepedonicus and Candida albicans , respectively. Compounds 1 – 3 exhibited moderate inhibitory activities against the lipopolysaccharide (LPS)-induced intracellular IL-6 production of murine macrophage cell line RAW264.7. [ABSTRACT FROM AUTHOR]

A new tetrasaccharide derivative, actinotetraose L (1), was isolated from the methanol extract of the mycelia of the grasshopper-associated rare actinobacteriumAmycolatopsissp. HCa1. The structure of the new compound was elucidated by a combination of 1D, 2D NMR (HMQC, HMBC, COSY, and NOESY), and HR-ESI-MS analyses asO-{3,4-di-O-[(E)-2-ethyl-2-butenoyl]- β-D-glucopyranosyl-(1 → 2)}-O-{3,4-di-O-[(E)-2-methyl-2-butenoyl]-β-D-glucopyranosyl-(1 → 2)}-6,6-di-O-[(E)-2-methyl-2-butenoyl]-α-D-glucopyranosyl-(1 → 1)-α-D-glucopyranoside. The immunosuppressive activity and cytotoxicity of the compound were evaluated by T-cell viability and MTT assays. Nonetheless, no significant activity was observed. [ABSTRACT FROM PUBLISHER]

Three new simple trichothecenes, 15-acetyltrichoverrol B ( 3), 13′-acetyltrichoverrin B ( 5), and 6′-dehydroxytrichoverrin B ( 6), along with five known trichothecenes trichodermadienediol B ( 1), trichoverrol B ( 2), trichoverrin B ( 4), and roridins A ( 7) and D ( 8), have been isolated from the liquid culture of Myrothecium roridum (strain no. QB-1). The structures of the new compounds were established by comprehensive analysis of 1D- and 2D-NMR data. All the compounds were evaluated for antifungal activity, only compounds 7 and 8 showed significant antifungal activity against the tested fungi ( MIC ranged from 10 to 5 μg/ml). [ABSTRACT FROM AUTHOR]

Five new prenylated diphenyl ethers ( 1 – 5 ), five known ones ( 6 – 10 ), and three xanthones ( 11 – 13 ), together with three anthraquinone derivatives ( 14 – 16 ), were obtained from the mantis-associated fungus Aspergillus versicolor GH-2. Their structures were elucidated on the basis of spectroscopic methods. The (2″ S ) absolute configuration of 1 was assigned by using the modified Mosher ester method. The known compounds 9 and 12 exhibited antibacterial activity against the clinical strain Streptococcus pyogenes with the MIC values of 2.5 and 5.0 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

The conversion from triene- to diene-typedansamycins is clarifiedstep by step in Streptomyces seoulensisIFB-A01.Such an intertype convertibility is adopted to establish for the firsttime the simultaneous mutasynthesis of both types of C17-benzene ansamycins(C17BAs). Three of the newly generated unnatural compounds showedpotent cytotoxicity. [ABSTRACT FROM AUTHOR]

Two new tricycloalternarenes I (1) and J (2), together with five known derivatives (3–7), were isolated from the culture of marine fungus Alternaria sp. The structures were elucidated by a combination of spectroscopic approach (1H, 13C NMR, HMBC, COSY, and NOESY) and the low-temperature (100 K) single-crystal X-ray crystallography analysis. The antimicrobial assays of tricycloalternarenes I (1) and J (2) were tested. [ABSTRACT FROM AUTHOR]

Highlights: [•] The endophyte Lasiodiplodia pseudotheobromae F2 produces six sulfur-containing diketopiperazines (1–6). [•] Lasiodipline E (5) was active against a panel of clinical bacterial pathogens. [•] Compounds 4 and 6 exemplified two previously unknown examples of cyclodipeptide structured type. [ABSTRACT FROM AUTHOR]

The limited selection of immunosuppressants in the clinic hampers the efficient management of immune disorders such as rejections after organ transplantations. However, the search for new immunosuppressive compounds remains random and creates inevitably financial and laborious wastes. Herein, we present an immunity-inspired discovery strategy that rationally allows an efficient identification of immunosuppressive compounds from the endophyte culture, as exemplified by the new peptide trichomide A. This compound exerts its immunosuppressive action more selectively than cyclosporin A. It was found that trichomide A decreases the expression of Bcl-2, increases the expression of Bax, and has a small or negligible effect on the expressions of p-Akt, CD25, and CD69. Our study strengthens the idea that the cross-kingdom similarity in immunity among living things could provide a shorter route towards the identification of natural products valuable for the development of new immunosuppressants. [ABSTRACT FROM AUTHOR]

Chemical study of the ethyl acetate extract of the plant endophytic fungus Cladosporium sp. (strain no. IFB3lp-2) yielded three new polyketides (1–3), together with nine known compounds. All of the structures were elucidated on the basis of spectroscopic methods. The isolated compounds were screened for their cytotoxic, antiviral, and acetyl cholinesterase inhibitory activities. Regretfully, no compounds showed any significant activity in these assays. [ABSTRACT FROM AUTHOR]

Abstract: A phytochemical study of Cryptocarya maclurei led to isolation of five flavanones, cryptogiones G–H, and a polyketide, cryptomaclurone. The structures of the isolates were elucidated by analysis of the 1D and 2D NMR spectroscopic data, and their absolute configurations were determined by CD methods. A putative biosynthetic pathway to them is proposed. Cytotoxicity of these compounds evaluated against KB, SGC-7901 and SW 1116 cancer cell lines, with only cryptomaclurone exhibiting moderate cytotoxicity (IC50 28.2, 28.4 and 16.4μM, respectively). [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The radices of Glycyrrhiza uralensis Fisch. and herbal preparations containing Glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in China. Glycyrrhizic acid (GA) is considered the principal component in Glycyrrhiza spp. with a wide spectrum of antiviral activity. Aim: The present study attempt to validate the medicinal use of Glycyrrhiza uralensis for hand, foot and mouth disease (HFMD) and further to verify whether GA is an active antiviral component in the water extract of Glycyrrhiza uralensis. Materials and methods: Radices of Glycyrrhiza uralensis Fisch. were extracted with hot water. The chemical contents of the extract were profiled with HPLC analysis. The antiviral activity of the extract and the major components was evaluated against infection of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) on Vero cells. The cytopathic effect caused by the infection was measured with MTT assay. Infectious virion production was determined using secondary infection assays and viral protein expression by immunoblotting analysis. Results: The extract at 1000μg/ml suppressed EV71 replication by 1.0 log and CVA16 by 1.5 logs. The antiviral activity was associated with the content of GA in the extract since selective depletion of GA from the extract by acid precipitation resulted in loss of antiviral activity. In contrast, the acid precipitant retained antiviral activity. The precipitant at a concentration of 200μg/ml inhibited EV71 and CVA16 replication by 1.7 and 2.2 logs, respectively. Furthermore, GA dose-dependently blocked viral replication of EV71 and CVA16. At 3mM, GA reduced infectious CVA16 and EV71 production by 3.5 and 2.2 logs, respectively. At 5mM, CVA16 production was reduced by 6.0 logs and EV71 by 4.0 logs. Both EV71 and CVA16 are members of Enterovirus genus, time-of-drug addition studies however showed that GA directly inactivated CVA16, while GA anti-EV71 effect was associated with an event(s) post virus cell entry. Conclusions: This study validated the medicinal usefulness of radices Glycyrrhiza uralensis against the etiological agents of HFMD. In addition to the identification of GA as the antiviral component of Glycyrrhiza uralensis against EV71 and CVA16 infection, this study also reveals that GA inhibits EV71 and CVA16 with distinct mechanisms. [Copyright &y& Elsevier]

A new alkaloid was isolated from the ethyl acetate extract of the culture of a termite-associated Streptomyces koyangensis BY-4. The structure of 1 was elucidated by using MS, NMR, electronic circular dichroism data, and computational approaches. Compound 1 showed weak antimicrobial activities against a panel of test microbes. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. [Copyright &y& Elsevier]

Abstract: One new angucyclinone derivative, amycomycin A (1), and one new angucycline, amycomycin B (2), along with 5 known compounds (3–7), were isolated from an actinobacterium Amycolatopsis sp. HCa1 associated with the grasshopper, Oxya chinensis. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR spectra. Compounds 1–7 were tested in vitro for their cytotoxic effects on five cell lines including human gastric adenocarcinoma cell line (BGC823), human hepatocarcinoma cell line (HepG2), human melanoma cell line (A375), human oral squamous carcinoma cell line (KB), and ghost cell line (Ghost-R5X4). Cell viability assays showed that compound 7 was active in four cell lines with IC50 values less than 18.0μM except in KB showing no activity up to 100μM. [Copyright &y& Elsevier]

Abstract: Stilbenoids including resveratrol contain the basic structural unit of 1,2-diphenylethylene. Naturally occurring stilbenoids have broad structural features due to oligomerization and modifications and some have demonstrated potent biological activities. In an effort to identify bioactive stilbenoids, we screened a group of dimeric and oligomeric stilbenoids against HSV-1 and HSV-2 infection. Several trimeric and tetrameric derivatives showed anti-herpetic activity at single digit micromolar concentrations. HSV-1 and HSV-2 replication requires for NF-κB and MAPK activation. The compounds showed no inhibitory activity against NF-κB and Erk/MAPK activation, instead those compounds promoted rapid and transient release of reactive oxygen species (ROS). Addition of N-acetylcysteine (NAC), a scavenger of ROS, reversed the inhibitory effect of those compounds against HSV replication. In addition to the identification of resveratrol derivatives with potent anti-HSV activity, our results uncover a mechanism of polyphenol-mediated anti-HSV response, linking anti-herpetic activity of oligomeric stilbenoids to innate immunity. [Copyright &y& Elsevier]

Abstract: Six flavonoids named cryptogiones A–F, and nine known compounds were isolated from an ethanol extract of stems of Cryptocarya chingii. The structures of the compounds were elucidated by interpretation of comprehensive spectroscopic data and X-ray analysis. A majority of these flavonoids contained an acetic acid/lactone moiety, a possible taxonomic marker. Anti-inflammatory effects of the compounds were evaluated using in vitro assays. At 20μM concentration, three compounds significantly inhibited TNFα-induced NF-кB activation and LPS-induced IL-1β expression. [Copyright &y& Elsevier]

The chemical study of endophytic fungus of Cochliobolus led to the isolation of 10 terpenes (1-10), including one new compound named isocochlioquinone B (1). Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. Compounds 5-7 showed significant neuraminidase inhibitory activity with IC50 values of 0.79-1.75 μM. [ABSTRACT FROM AUTHOR]

Abstract: Eleven C2-substituted derivatives of resveratrol (trans-3,4′,5-trihydroxystilbene, RES) were prepared by partial synthesis from RES and evaluated for their cytotoxic activities against a human nasopharyngeal epidermoid tumor cell line KB. Among them, compounds 2 and 3 were more active than 5-fluorouracil (5-FU), an anticancer drug, and compound 5f exhibited similar activity to 5-FU. On the basis of the biological results, structure–activity relationships were discussed. [Copyright &y& Elsevier]

• One new kynurenine-containing cyclic heptapeptide named unguisin G was isolated from the sponge-derived fungus. • The structure was elucidated by the spectroscopic data of HRESIMS and NMR. • The absolute configuration of unguisin G was confirmed by Marfey's reaction. One new cyclic heptapeptide containing non-proteinogenic amino acid residues kynurenine and γ -aminobutyric acid, named unguisin G, as well as three known congeners unguisins A, E and F, were isolated from a sponge-derived fungus Aspergillus candidus NF2412. The structures were elucidated by comprehensive spectroscopic analyses of HRESIMS and NMR data. The absolute configuration of amino acid residues of 1 was determined by advanced Marfey's method. All compounds were evaluated on antimicrobial activities against nine pathogens by the agar diffusion method. [ABSTRACT FROM AUTHOR]