Multienzyme Cascade Catalyzed Skeleton Rearrangement in a Caged Polyketide Biosynthesis.

Rearrangement of the skeleton is crucial for improving the structural complexity and diversity of type II polyketide natural products. In this study, we investigated the rearrangement process from a planar aromatic tetracyclic intermediate to the caged lactones, which is managed by five oxidoreductases. We chemically synthesized the proposed linear tetracyclic substrate, validated the transformation process through and experiments, and elucidated the enzyme-catalyzed mechanism using isotope labeling.

Photochemistry of microplastics-derived dissolved organic matter: Reactive species generation and organic pollutant degradation.

Dissolved organic matter (DOM) originating from microplastics (MPs-DOM) is increasingly recognized as a substantial component of aquatic DOM. The photochemistry of MPs-DOM, essential for understanding its environmental fate and impacts, remains largely unexplored. This study investigates the photochemical behaviors of MPs-DOM derived from two common plastics: polystyrene (PS) and polyvinyl chloride (PVC), which represent aromatic and aliphatic plastics, respectively.

Different DNA Binding and Damage Mode between Anticancer Antibiotics Trioxacarcin A and LL-D49194α1.

Trioxacarcin A (TXN) is a highly potent cytotoxic antibiotic with remarkable structural complexity. The crystal structure of TXN bound to double-stranded DNA (dsDNA) suggested that the TXN interaction might depend on positions of two sugar subunits on the minor and major grooves of dsDNA. LL-D49194α1 (LLD) is a TXN analogue bearing the same polycyclic polyketide scaffold with a distinct glycosylation pattern.

Direct evidence for the occurrence of indigenous cadmium-based nanoparticles in paddy soils.

Speciation of heavy metal-based nanoparticles (NPs) in paddy soils greatly determines their fate and potential risk towards food safety. However, quantitative understanding of such distinctive species remains challenging, because they are commonly presented at trace levels (e.g.

Efficacy and Functional Mechanisms of a Two-Stage Pretreatment Approach Based on Alkali and Ionic Liquid for Bioconversion of Waste Medium-Density Fiberboard.

A novel pretreatment strategy utilizing a combination of NaOH and 1-Butyl-3-methylimidazolium chloride ([Bmim]Cl) was proposed to enhance the enzymatic hydrolysis of abandoned Medium-density fiberboard (MDF). The synergistic effect of NaOH and [Bmim]Cl pretreatment significantly improved the glucose yield, reaching 445.8 mg/g within 72 h, which was 5.

Deciphering fluorescent and molecular fingerprint of dissolved organic matter leached from microplastics in water.

Despite extensive research into the presence and behavior of microplastics (MPs) in the environment, limited attention has been given to the investigation of the characteristics of dissolved organic matter (DOM) that leaches from MPs (MPs-DOM). Herein, two frequently encountered plastic particles in aquatic environments, specifically polyethylene terephthalate (PET)- and polyethylene (PE)-MPs, were subjected to leaching in the aquatic settings for seven days, both in the absence of light and under UV irradiation. Measurements of dissolved organic carbon (DOC) indicated that UV exposure enhanced the liberation of DOM from PET-MPs, while PE-MPs did not exhibit such leaching.

Trioxacarcin A Interactions with G-Quadruplex DNA Reveal Its Potential New Targets as an Anticancer Agent.

Trioxacarcin (TXN) A was reported to be an anticancer agent through alkylation of dsDNA. G-quadruplex DNA (G4-DNA) is frequently formed in the promoter regions of oncogenes and the ends of telomerase genes, considered as promising drug targets for anticancer therapy. There are no reports about TXN A interactions with G4-DNA.

Phenol Liquefaction of Waste Sawdust Pretreated by Sodium Hydroxide: Optimization of Parameters Using Response Surface Methodology.

In this study, a two-step method was used to realize the liquefaction of waste sawdust under atmospheric pressure, and to achieve a high liquefaction rate. Specifically, waste sawdust was pretreated with NaOH, followed by liquefaction using phenol. The relative optimum condition for alkali-heat pretreatment was a 1:1 mass ratio of NaOH to sawdust at 140 °C.

Biosynthesis of DNA-Alkylating Antitumor Natural Products.

DNA-alkylating natural products play an important role in drug development due to their significant antitumor activities. They usually show high affinity with DNA through different mechanisms with the aid of their unique scaffold and highly active functional groups. Therefore, the biosynthesis of these natural products has been extensively studied, especially the construction of their pharmacophores.

Base excision repair system targeting DNA adducts of trioxacarcin/LL-D49194 antibiotics for self-resistance.

Two families of DNA glycosylases (YtkR2/AlkD, AlkZ/YcaQ) have been found to remove bulky and crosslinking DNA adducts produced by bacterial natural products. Whether DNA glycosylases eliminate other types of damage formed by structurally diverse antibiotics is unknown. Here, we identify four DNA glycosylases-TxnU2, TxnU4, LldU1 and LldU5-important for biosynthesis of the aromatic polyketide antibiotics trioxacarcin A (TXNA) and LL-D49194 (LLD), and show that the enzymes provide self-resistance to the producing strains by excising the intercalated guanine adducts of TXNA and LLD.

A ratiometric fluorescent probe for the quantitative detection of styrene in air.

A ratiometric fluorescent probe (N-butyl-4-(4-amino-styryl)-1,8-naphthalimide) was developed for the quantitative detection of styrene in air. The sensing mechanism was found to involve a Heck reaction between the pretreated probe (diazotization) and styrene. A probe solution absorption method was established to detect gaseous styrene quantitatively.

Activation and Characterization of Cryptic Gene Cluster: Two Series of Aromatic Polyketides Biosynthesized by Divergent Pathways.

One biosynthetic gene cluster (BGC) usually governs the biosynthesis of a series of compounds exhibiting either the same or similar molecular scaffolds. Reported here is a multiplex activation strategy to awaken a cryptic BGC associated with tetracycline polyketides, resulting in the discovery of compounds having different core structures. By constitutively expressing a positive regulator gene in tandem mode, a single BGC directed the biosynthesis of eight aromatic polyketides with two types of frameworks, two pentacyclic isomers and six glycosylated tetracyclines.

Discovery of Druggability-Improved Analogues by Investigation of the LL-D49194α1 Biosynthetic Pathway.

The biosynthetic gene cluster of antitumor antibiotic LL-D49194α1 (LLD) was identified and comparatively analyzed with that of trioxacarcins. The tailoring genes encoding glycosyltransferase, methyltransferase and cytochrome P450 were systematically deleted, which led to the discovery of eight compounds from the mutants. Preliminary pharmaceutical evaluation revealed two intermediates exhibiting higher cytotoxicity, stability and solubility.

A microwave-assisted aqueous ionic liquid pretreatment to enhance enzymatic hydrolysis of Eucalyptus and its mechanism.

A novel pretreatment strategy based on combination of microwave and ionic liquid [TBA][OH] was developed for enhancing enzymatic hydrolysis of Eucalyptus sawdust. The sugar yield of pretreated sample achieved 410.67 mg/g in 48 h, which suffered from optimized microwave-assisted [TBA][OH] pretreatment.

Enzymology of Anthraquinone-γ-Pyrone Ring Formation in Complex Aromatic Polyketide Biosynthesis.

Aromatic-fused γ-pyrones are structural features of many bioactive natural products and valid scaffolds for medicinal chemistry. However, the enzymology of their formation has not been completely established. Now it is demonstrated that TxnO9, a CalC-like protein belonging to a START family, functions as an unexpected anthraquinone-γ-pyrone synthase involved in the biosynthesis of antitumor antibiotic trioxacarcin A (TXN-A).

Comparison of ultrasound-assisted ionic liquid and alkaline pretreatment of Eucalyptus for enhancing enzymatic saccharification.

Two ultrasound-assisted pretreatment technologies, ultrasound-assisted alkaline and ultrasound-assisted aqueous ionic liquid tetrabutylammonium hydroxide ([TBA][OH]), are compared systematically in regard to enzymatic saccharification. Pretreated Eucalyptus samples were characterized by powder X-ray diffraction, C cross polarization/magic-angle spinning solid state NMR spectroscopy, Fourier transform infrared spectroscopy, Scanning electron microscope (SEM) and chemistry composition analysis. These results not only explain the enzymatic saccharification difference between samples from the microstructure level, but also provide helpful information for relevant pretreatment research.

[Sesquiterpenes from stems of Schisandra henryi var. henryi].

The dried stems of Schisandra henryi var. henryi were extracted with 95% ethanol and the extracts were further subjected to partition, affording the ethyl acetate extracts(EtOAc Extrs.).

A novel single-fluorophore-based ratiometric fluorescent probe for direct detection of isocyanates in air.

A ratiometric fluorescent probe based on anthracene carboximide was developed for direct detection of isocyanates in air. The sensing mechanism was illustrated to be variation in the photophysical properties caused by the nucleophilic reaction of the probe molecule. A number of isocyanates were conveniently detected by a test paper.

Fluorescent nanoprobe for in-vivo ratiometric imaging of endogenous hydrogen peroxide resulted from drug-induced organ damages.

Drug-induced organ damages have been considered as a grave problem regarding public health; hence effective method for in vivo detection of drug-induced organ damages is of great significance. Herein we developed a ratiometric fluorescent nanoprobe (NPs-A), which was prepared by loading the probe molecules into phospholipid bilayer, for assaying hydrogen peroxide (HO, an organ damage biomarker) level in vivo. The photophysical behavior of the probe molecule depends on the electron-withdrawing ability of the group at the 6- position of anthracene ring, on which the recognition moiety for hydrogen peroxide (dicarbonyl coupled with nitrophenyl, referred to as nitrophenyl-dicarbonyl) was introduced.

A fluorescent assay for γ-glutamyltranspeptidase via aggregation induced emission and its applications in real samples.

γ-Glutamyl transpeptidase (GGT) plays crucial roles in some physiological processes. Herein a turn-on fluorescent probe for γ-glutamyl transpeptidase (GGT) assay based on aggregation-induced-emission (AIE) effect and the enzyme-induced transformation of hydrophilicity to hydrophobicity has been developed by functionalizing tetraphenylethylene (TPE) derivative with two γ-glutamyl amide groups, which simultaneously work as recognition units and hydrophilic groups. When the γ-glutamyl amide groups are cleaved through GGT enzymatic reaction, the hydrophobic reaction product readily aggregate and correspondingly strong blue fluorescence can be observed, as a result of activated AIE process.

The SARP Family Regulator Txn9 and Two-Component Response Regulator Txn11 are Key Activators for Trioxacarcin Biosynthesis in Streptomyces bottropensis.

Trioxacarcin A is a polyoxygenated, structurally complex antibiotic produced by Streptomyces spp., which possesses high anti-bacterial, anti-malaria, and anti-tumor activities. The trioxacarcin biosynthetic pathway involves type II polyketide synthases (PKSs) with L-isoleucine as a unique starter unit, as well as many complex post-PKS tailoring enzymes and resistance and regulatory proteins.

Biosynthesis of trioxacarcin revealing a different starter unit and complex tailoring steps for type II polyketide synthase.

Trioxacarcins (TXNs) are highly oxygenated, polycyclic aromatic natural products with remarkable biological activity and structural complexity. Evidence from C-labelled precursor feeding studies demonstrated that the scaffold was biosynthesized from one unit of l-isoleucine and nine units of malonyl-CoA, which suggested a different starter unit in the biosynthesis. Genetic analysis of the biosynthetic gene cluster revealed 56 genes encoding a type II polyketide synthase (PKS), combined with a large amount of tailoring enzymes.

A ratiometric fluorescent probe for in vivo tracking of alkaline phosphatase level variation resulting from drug-induced organ damage.

Clinical drug-induced organ toxicity and damage have been recognized as an important public health issue, and an effective approach capable of in vivo detection of biomarkers resulting from drug-induced organ damage is being actively pursued. Herein, we demonstrate a ratiometric fluorescent probe that can trace the variation in alkaline phosphatase (ALP, an organ damage biomarker) levels spatially in vivo. The probe was synthesized by incorporating a phosphate group and an amine-N-oxide group on a 1,8-naphthalimide derivative.

Ratiometric fluorescence assay for γ-glutamyltranspeptidase detection based on a single fluorophore via analyte-induced variation of substitution.

The first ratiometric fluorescent probe for γ-glutamyltranspeptidase (GGT) was developed, which functions through GGT-induced variation of substitution and subsequent changes in photophysical properties. It can detect GGT in human serum, and be used to visualize the endogenous GGT in ovarian cancer cells.

Carbon-dot-based fluorescent turn-on sensor for selectively detecting sulfide anions in totally aqueous media and imaging inside live cells.

Sulfide anions are generated not only as a byproduct from industrial processes but also in biosystems. Hence, robust fluorescent sensors for detecting sulfide anions which are fast-responding, water soluble and biocompatible are highly desirable. Herein, we report a carbon-dot-based fluorescent sensor, which features excellent water solubility, low cytotoxicity and a short response time.