Evolution of orphan and atypical histidine kinases and response regulators for microbial signaling diversity.

Two-component signaling systems (TCS) are the predominant means of microbes for sensing and responding to environmental stimuli. Typically, TCS is comprised of a sensor histidine kinase (HK) and a cognate response regulator (RR), which might have coevolved together. They usually involve the phosphoryl transfer signaling mechanism.

Diverse evolutionary origins of microbial [4 + 2]-cyclases in natural product biosynthesis.

Natural [4 + 2]-cyclases catalyze concerted cycloaddition during biosynthesis of over 400 natural products reported. Microbial [4 + 2]-cyclases are structurally diverse with a broad range of substrates. Thus far, about 52 putative microbial [4 + 2]-cyclases of 13 different types have been characterized, with over 20 crystal structures.

Inhibition of inflammation by SP600125 in cholestatic liver injury is dependent on the administration‑based exposure profile.

SP600125 is a classic inhibitor of c‑Jun‑N‑terminal kinase (JNK) that is widely used in numerous medicinal studies, but its administration regimen has yet to be optimized. In the present study, intraperitoneal (i.p.

[The cholestatic fibrosis induced by α-naphthylisothiocyanate in mice and the inflammation pathway].

To explore the development of cholestatic fibrosis induced by α-naphthylisothiocyanate (ANIT) and the inflammation pathways. Fifteen 129/Sv mice weighing (23±2) g were randomly divided into 2 groups: control group (=5) and experiment group (=10). The control group was fed commercial chow diet and the experiment group was fed the same diet supplemented with 0.

Cholestatic models induced by lithocholic acid and α‑naphthylisothiocyanate: Different etiological mechanisms for liver injury but shared JNK/STAT3 signaling.

α‑naphthylisothiocyanate (ANIT) is used to induce intrahepatic cholestasis and it is frequently used for investigations into the disease mechanism. The lithocholic acid (LCA) cholestatic model has also been extensively used in various studies; however, to the best of our knowledge, a comparative study determining the hepatotoxic mechanisms induced by these two models has not been previously conducted. In the present study, ICR mice were treated with ANIT or LCA to induce cholestatic liver injury.

Therapeutic action against chronic cholestatic liver injury by low-dose fenofibrate involves anti-chemotaxis via JNK-AP1-CCL2/CXCL2 signaling.

Background: Fenofibrate was reported to be beneficial for cholestasis in combination with ursodeoxycholic acid. However, its therapeutic action as single therapy for chronic cholestasis and the underlying mechanism are not known.

Methods: In the present study, wild-type (WT) mice were administered a 0.

Evolution of LuxR solos in bacterial communication: receptors and signals.

Cell-cell communication in bacteria needs chemical signals and cognate receptors. Many Gram-negative bacteria use acyl-homoserine lactones (AHLs) and cognate LuxR-type receptors to regulate their quorum sensing (QS) systems. The signal synthase-receptor (LuxI-LuxR) pairs may have co-evolved together.

Regulatory and evolutionary roles of pseudo γ-butyrolactone receptors in antibiotic biosynthesis and resistance.

Bacteria modulate their physiological behavior by responding to various signal molecules. The signals are received by cognate receptors, which usually mediate transcriptional regulation. Streptomyces employ γ-butyrolactones (GBLs) and cognate GBL receptors (GblRs) to regulate secondary metabolism and morphological development.

20-Nor-Isopimarane Epimers Produced by SD-310, a Fungal Strain Obtained from Deep Sea Sediment.

Four new uncommon 20-nor-isopimarane diterpenoid epimers, aspewentins I-L (⁻), together with a new methylated derivative of , aspewentin M (), were isolated from the deep sea sediment-derived fungus SD-310. The very similar structures of these epimers made the separation and purification procedures difficult. The structures of compounds ⁻ were illustrated based on spectroscopic analysis, and the absolute configurations of compounds ⁻ were unambiguously determined by the combination of NOESY, time-dependent density functional (TDDFT)-ECD calculations, and X-ray crystallographic analysis.

Basal PPARα inhibits bile acid metabolism adaptation in chronic cholestatic model induced by α-naphthylisothiocyanate.

Cholestasis is one of the most challenging diseases to be treated in current hepatology. However little is known about the adaptation difference and the underlying mechanism between acute and chronic cholestasis. In this study, wild-type and Pparα-null mice were orally administered diet containing 0.

PPARα-independent action against metabolic syndrome development by fibrates is mediated by inhibition of STAT3 signalling.

Objectives: Metabolic syndrome (MS) is the concurrence of at least three of five medical conditions: obesity, high blood pressure, insulin resistance, high serum triglyceride (TG) and low serum high-density lipoprotein levels. While fibrates are used to treat disorders other than the lowering serum TG, the mechanism by which fibrates decrease MS has not been established.

Methods: In this study, wild-type and Ppara-null mice fed a medium-fat diet (MFD) were administered gemfibrozil and fenofibrate for 3 months respectively, to explore the effect and action mechanism.

Antibacterial anthraquinone derivatives isolated from a mangrove-derived endophytic fungus Aspergillus nidulans by ethanol stress strategy.

Three new natural products, including a new anthraquinone derivative isoversicolorin C (1), a new xanthone analog isosecosterigmatocystin (2), and a new amino acid derivative, glulisine A (3), along with six related metabolites (4-9) were isolated from the culture broth and mycelia extracts of the mangrove-derived endophytic fungus Aspergillus nidulans MA-143 under 0.1% ethanol stress. Their structures were elucidated by detailed analysis of their NMR spectra, ECD spectrum, and X-ray crystallographic experiments.

The plant hormone abscisic acid regulates the growth and metabolism of endophytic fungus Aspergillus nidulans.

Plant hormones are well known chemical signals that regulate plant growth, development, and adaptation. However, after comparative transcriptome and metabolite analysis, we found that the plant hormone abscisic acid (ABA) also affect the growth and metabolism of endophytic fungus Aspergillus nidulans. There were 3148 up-regulated and 3160 down-regulated genes identified during 100 nM ABA induction.

Targeted Metabolomics Reveals a Protective Role for Basal PPARα in Cholestasis Induced by α-Naphthylisothiocyanate.

α-Naphthylisothiocyanate (ANIT) is an experimental agent used to induce intrahepatic cholestasis. The Ppara-null mouse line is widely employed to explore the physiological and pathological roles of PPARα. However, little is known about how PPARα influences the hepatotoxicity of ANIT.

Inhibition of JNK signalling mediates PPARα-dependent protection against intrahepatic cholestasis by fenofibrate.

Background And Purpose: Fenofibrate, a PPARα agonist, is the most widely prescribed drug for treating hyperlipidaemia. Although fibrate drugs are reported to be beneficial for cholestasis, their underlying mechanism has not been determined.

Experimental Approach: Wild-type mice and Pparα-null mice were pretreated orally with fenofibrate for 3 days, following which α-naphthylisothiocyanate (ANIT) was administered to induce cholestasis.

Peroxisome Proliferator-Activated Receptor α Activation Suppresses Cytochrome P450 Induction Potential in Mice Treated with Gemfibrozil.

Gemfibrozil, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely used for hypertriglyceridaemia and mixed hyperlipidaemia. Drug-drug interaction of gemfibrozil and other PPARα agonists has been reported. However, the role of PPARα in cytochrome P450 (CYP) induction by fibrates is not well known.

Relationships between the Regulatory Systems of Quorum Sensing and Multidrug Resistance.

Cell-cell communications, known as quorum sensing (QS) in bacteria, involve the signal molecules as chemical languages and the corresponding receptors as transcriptional regulators. In Gram-negative bacteria, orphan LuxR receptors recognize signals more than just acylhomoserine lactones, and modulate interspecies and interkingdom communications. Whereas, in the Gram-positive Streptomyces, pseudo gamma-butyrolactones (GBLs) receptors bind antibiotics other than GBL signals, and coordinate antibiotics biosynthesis.

Tetranorlabdane Diterpenoids from the Deep Sea Sediment-Derived Fungus Aspergillus wentii SD-310.

Two new tetranorlabdane diterpenoids, asperolides D (1) and E (2), along with six related known congeners (3-8), were isolated and identified from the culture extract of the deep sea sediment-derived fungus Aspergillus wentii SD-310. The structures of these compounds were established on the basis of spectroscopic interpretation, and the skeleton and absolute configurations of asperolides D (1) and E (2) were determined by X-ray crystallographic analysis. Compounds 1 and 2 were evaluated for their cytotoxic activity against seven tumor cell lines and antibacterial activity against two human and eight aquatic pathogens.

Independent Evolution of Six Families of Halogenating Enzymes.

Halogenated natural products are widespread in the environment, and the halogen atoms are typically vital to their bioactivities. Thus far, six families of halogenating enzymes have been identified: cofactor-free haloperoxidases (HPO), vanadium-dependent haloperoxidases (V-HPO), heme iron-dependent haloperoxidases (HI-HPO), non-heme iron-dependent halogenases (NI-HG), flavin-dependent halogenases (F-HG), and S-adenosyl-L-methionine (SAM)-dependent halogenases (S-HG). However, these halogenating enzymes with similar biological functions but distinct structures might have evolved independently.

Aspewentins D-H, 20-Nor-isopimarane Derivatives from the Deep Sea Sediment-Derived Fungus Aspergillus wentii SD-310.

Five new 20-nor-isopimarane diterpenoids, aspewentins D-H (1-5), along with a related known congener, aspewentin A (6), were isolated from the culture extract of Aspergillus wentii SD-310, a fungal strain obtained from a deep-sea sediment sample. The structures of these compounds were established on the basis of spectroscopic interpretation, and the absolute configurations of compounds 1-5 were determined by X-ray crystallographic analysis and TDDFT-ECD calculations. The isolated compounds were evaluated for antimicrobial activity against nine human and aquatic pathogenic bacteria and four plant pathogenic fungi as well as for lethality against brine shrimp (Artemia salina).

Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones.

The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields.

Citrifelins A and B, Citrinin Adducts with a Tetracyclic Framework from Cocultures of Marine-Derived Isolates of Penicillium citrinum and Beauveria felina.

Citrifelins A (1) and B (2), two citrinin adducts possessing a unique tetracyclic framework, were characterized from a coculture of marine-derived fungal isolates of Penicillium citrinum and Beauveria felina. Neither fungus produced these compounds when cultured alone under the same conditions. The structures of these adducts were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assigned on the basis of TDDFT-ECD calculations.

Bisthiodiketopiperazines and Acorane Sesquiterpenes Produced by the Marine-Derived Fungus Penicillium adametzioides AS-53 on Different Culture Media.

Chemical investigation of the marine-sponge-derived fungus Penicillium adametzioides AS-53 resulted in the identification of two new bisthiodiketopiperazine derivatives, adametizines A (1) and B (2), from cultivation in a liquid potato-dextrose broth (PDB) culture medium, whereas two new acorane sesquiterpenes, adametacorenols A (3) and B (4), were isolated from a rice solid culture medium. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The absolute configuration of compound 1 was determined by X-ray crystallographic analysis, and that of 3 was determined by modified Mosher's method.

Antimicrobial Phenolic Bisabolanes and Related Derivatives from Penicillium aculeatum SD-321, a Deep Sea Sediment-Derived Fungus.

Three new phenolic bisabolane sesquiterpenes, peniciaculins A (1) and B (2) and (7S)-(-)-10-hydroxysydonic acid (3), together with a new nor-bisabolane derivative, 1-hydroxyboivinianin A (4), as well as six known bisabolanes (5-10), were identified from the culture of Penicillium aculeatum SD-321, a fungus isolated from deep-sea sediments. The structures of these compounds were mainly determined by analysis of spectroscopic data, and the absolute configurations of compounds 1-4 were established by comparing their ECD spectra with those of known analogues or by TDDFT-ECD calculations. Compound 1 represents the first example of a bisabolane analogue linked to a diphenyl ether moiety via an ether bond, while compound 2 appears to be the first dimeric bisabolane analogue where the two monomers are coupled to each other via an ester bond.

Rubrumazines A-C, Indolediketopiperazines of the Isoechinulin Class from Eurotium rubrum MA-150, a Fungus Obtained from Marine Mangrove-Derived Rhizospheric Soil.

Three new indolediketopiperazine alkaloids of the isoechinulin type, rubrumazines A-C (1-3), each possessing an oxygenated prenyl group either at C-7 (1 and 2) or at C-5 (3), along with 13 related analogues (4-16), were isolated and identified from a culture extract of Eurotium rubrum MA-150, a fungus obtained from mangrove-derived rhizospheric soil collected from the Andaman Sea coastline, Thailand. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometry data analysis. The structure and absolute configuration of compound 1 were confirmed by X-ray crystallographic analysis, thus providing the first characterized crystal structure of an isoechinulin-type alkaloid.