The Biosynthesis of the Aroma Volatile 2‐Methyltetrahydrothiophen‐3‐one in the Bacterium Chitinophaga Fx7914

2‐Methyltetrahydrothiophen‐3‐one ( 3 ) is a volatile compound that plays an important role especially in food and flavour chemistry because it contributes to the aroma of several foodstuffs including wine. Although 3 can be formed by chemical reactions during food preparation, it is also produced by microorganisms. Recent studies with yeasts showed that methionine ( 1 ) is a potential precursor of 3 , but the mechanism of the transformation is unknown. The biosynthetic pathway leading to 3 in the bacterium Chitinophaga Fx7914 was probed. Extensive feeding experiments with differently labelled precursors by using liquid cultures of Chitinophaga Fx7914 were performed. The volatiles released by the bacterium were collected by using a closed loop stripping apparatus (CLSA) and analysed by GC–MS. The observed incorporation pattern of the precursors into 3 led to the elucidation of the biosynthetic pathway. One part of the compound 2 originates from homocysteine ( 15 ), which is transformed into 3‐mercaptopropanal ( 17 ). The second biosynthetic building block is pyruvate ( 14 ). An acyloin‐forming reaction furnishes the key intermediate 21 , which cyclises intramolecularly to a diol. Dehydration followed by tautomerisation lead to the cyclic ketone 3 , which is produced by the bacterium in racemic form.     

Biosynthesis and the Roles of Plant Sterols in Development and Stress Responses

Plant sterols are important components of the cell membrane and lipid rafts, which play a crucial role in various physiological and biochemical processes during development and stress resistance in plants. In recent years, many studies in higher plants have been reported in the biosynthesis pathway of plant sterols, whereas the knowledge about the regulation and accumulation of sterols is not well understood. In this review, we summarize and discuss the recent findings in the field of plant sterols, including their biosynthesis, regulation, functions, as well as the mechanism involved in abiotic stress responses. These studies provide better knowledge on the synthesis and regulation of sterols, and the review also aimed to provide new insights for the global role of sterols, which is liable to benefit future research on the development and abiotic stress tolerance in plant.     

Plant sn‐Glycerol‐3‐Phosphate Acyltransferases: Biocatalysts Involved in the Biosynthesis of Intracellular and Extracellular Lipids

Acyl‐lipids such as intracellular phospholipids, galactolipids, sphingolipids, and surface lipids play a crucial role in plant cells by serving as major components of cellular membranes, seed storage oils, and extracellular lipids such as cutin and suberin. Plant lipids are also widely used to make food, renewable biomaterials, and fuels. As such, enormous efforts have been made to uncover the specific roles of different genes and enzymes involved in lipid biosynthetic pathways over the last few decades. sn‐Glycerol‐3‐phosphate acyltransferases (GPAT) are a group of important enzymes catalyzing the acylation of sn‐glycerol‐3‐phosphate at the sn‐1 or sn‐2 position to produce lysophosphatidic acids. This reaction constitutes the first step of storage‐lipid assembly and is also important in polar‐ and extracellular‐lipid biosynthesis. Ten GPAT have been identified in Arabidopsis, and many homologs have also been reported in other plant species. These enzymes differentially localize to plastids, mitochondria, and the endoplasmic reticulum, where they have different biological functions, resulting in distinct metabolic fate(s) for lysophosphatidic acid. Although studies in recent years have led to new discoveries about plant GPAT, many gaps still exist in our understanding of this group of enzymes. In this article, we highlight current biochemical and molecular knowledge regarding plant GPAT, and also discuss deficiencies in our understanding of their functions in the context of plant acyl‐lipid biosynthesis.     

Antipredator Defense of Biological Control Agent Oxyops vitiosa Is Mediated by Plant Volatiles Sequestered from the Host Plant Melaleuca quinquenervia

The weevil Oxyops vitiosa is an Australian species imported to Florida, USA, for the biological control of the invasive weed species Melaleuca quinquenervia. Larvae of this species feed on leaves of their host and produce a shiny orange secretion that covers the integument. When this secretion is applied at physiological concentrations to dog food bait, fire ant consumption and visitation are significantly reduced. Gas chromatographic analysis indicates that the larval secretion qualitatively and quantitatively resembles the terpenoid composition of the host foliage. When the combination of 10 major terpenoids from the O. vitiosa secretion was applied to dog food bait, fire ant consumption and visitation were reduced. When these 10 terpenoids were tested individually, the sesquiterpene viridiflorol was the most active component in decreasing fire ant consumption. Fire ant visitation was initially (15 min after initiation of the study) decreased for dog food bait treated with viridiflorol and the monoterpenes 1,8-cineole and -terpineol. Fire ants continued to avoid the bait treated with viridiflorol at 18 g/mg dog food for up to 6 hr after the initiation of the experiment. Moreover, ants avoided bait treated with 1.8 g/mg for up to 3 hr. The concentrations of viridiflorol, 1,8-cineole, and -terpineol in larval washes were about twice that of the host foliage, suggesting that the larvae sequester these plant-derived compounds for defense against generalist predators.     

A Cytochrome P450‐Mediated Intramolecular Carbon–Carbon Ring Closure in the Biosynthesis of Multidrug‐Resistance‐Reversing Lathyrane Diterpenoids

The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi‐jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon–carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6‐hydroxy‐5,9‐diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant.     

Improving the Search Performance of Extended Connectivity Fingerprints through Activity‐Oriented Feature Filtering and Application of a Bit‐Density‐Dependent Similarity Function

Improving fingerprint search performance : An activity‐oriented feature‐ filtering procedure and a corresponding similarity function were developed for molecule‐specific fingerprints, recording ensembles of structural patterns such as the popular extended connectivity fingerprints. Shown are comparisons of search calculations for cyclooxygenase inhibitors based on k nearest neighbor (1NN, 10NN) and Tanimoto coefficient (Tc) calculations, and the ACF BDM approach introduced herein.

     

Unlocking the Chemotherapeutic Potential of β‐Aminovinyl Ketones and Related Compounds

The role of β‐aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.

     

Crystal Structures of a Bioactive 6′‐Hydroxy Variant of Sisomicin Bound to the Bacterial and Protozoal Ribosomal Decoding Sites

Parasitic infections recognized as neglected tropical diseases are a source of concern for several regions of the world. Aminoglycosides are potent antimicrobial agents that have been extensively studied by biochemical and structural studies in prokaryotes. However, the molecular mechanism of their potential antiprotozoal activity is less well understood. In the present study, we have examined the in vitro inhibitory activities of some aminoglycosides with a 6′‐hydroxy group on ring I and highlight that one of them, 6′‐hydroxysisomicin, exhibits promising activity against a broad range of protozoan parasites. Furthermore, we have conducted X‐ray analyses of 6′‐hydroxysisomicin bound to the target ribosomal RNA A‐sites in order to understand the mechanisms of both its antibacterial and antiprotozoal activities at the molecular level. The unsaturated ring I of 6′‐hydroxysisomicin can directly stack on G1491, which is highly conserved in bacterial and protozoal species, through π–π interaction and fits closer to the guanidine base than the typically saturated and hydroxylated ring I of other structurally related aminoglycosides. Consequently, the compound adopts a lower energy conformation within the bacterial and protozoal A‐sites and makes pseudo pairs to either A or G at position 1408. The A‐site‐selective binding mode strongly suggests that 6′‐hydroxysisomicin is a potential lead for the design of next‐generation aminoglycosides targeting a wide variety of infectious diseases.     

Investigations into the Biosynthesis,Regulation, and Self‐Resistance of Toxoflavin in Pseudomonas protegens Pf‐5

Pseudomonas spp. are prolific producers of natural products from many structural classes. Here we show that the soil bacterium Pseudomonas protegens Pf‐5 is capable of producing trace levels of the triazine natural product toxoflavin ( 1 ) under microaerobic conditions. We evaluated toxoflavin production by derivatives of Pf‐5 with deletions in specific biosynthesis genes, which led us to propose a revised biosynthetic pathway for toxoflavin that shares the first two steps with riboflavin biosynthesis. We also report that toxM, which is not present in the well‐characterized cluster of Burkholderia glumae, encodes a monooxygenase that degrades toxoflavin. The toxoflavin degradation product of ToxM is identical to that of TflA, the toxoflavin lyase from Paenibacillus polymyxa. Toxoflavin production by P. protegens causes inhibition of several plant‐pathogenic bacteria, and introduction of toxM into the toxoflavin‐sensitive strain Pseudomonas syringae DC3000 results in resistance to toxoflavin.     

Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85‐8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases

Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH). HNE inhibitors should reestablish the protease–anti‐protease balance. By means of medicinal chemistry a novel dihydropyrimidinone lead‐structure class was identified. Further chemical optimization yielded orally active compounds with favorable pharmacokinetics such as the chemical probe BAY‐678. While maintaining outstanding target selectivity, picomolar potency was achieved by locking the bioactive conformation of these inhibitors with a strategically positioned methyl sulfone substituent. An induced‐fit binding mode allowed tight interactions with the S2 and S1 pockets of HNE. BAY 85‐8501 ((4S)‐4‐[4‐cyano‐2‐(methylsulfonyl)phenyl]‐3,6‐dimethyl‐2‐oxo‐1‐[3‐(trifluoromethyl)phenyl]‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile) was shown to be efficacious in a rodent animal model related to ALI. BAY 85‐8501 is currently being tested in clinical studies for the treatment of pulmonary diseases.     

Regulation of the Bud Dormancy Development and Release in Micropropagated Rhubarb ‘Malinowy’

Culinary rhubarb is a vegetable crop, valued for its stalks, very rich in different natural bioactive ingredients. In commercial rhubarb stalk production, the bud dormancy development and release are crucial processes that determine the yields and quality of stalks. To date, reports on rhubarb bud dormancy regulation, however, are lacking. It is known that dormancy status depends on cultivars. The study aimed to determine the dormancy regulation in a valuable selection of rhubarb ‘Malinowy’. Changes in carbohydrate, total phenolic, endogenous hormone levels, and gene expression levels during dormancy development and release were studied in micropropagated rhubarb plantlets. Dormancy developed at high temperature (25.5 °C), and long day. Leaf senescence and dying were consistent with a significant increase in starch, total phenolics, ABA, IAA and SA levels. Five weeks of cooling at 4 °C were sufficient to break dormancy, but rhizomes stored for a longer duration showed faster and more uniformity leaf growing, and higher stalk length. No growth response was observed for non-cooled rhizomes. The low temperature activated carbohydrate and hormone metabolism and signalling in the buds. The increased expression of AMY3, BMY3, SUS3, BGLU17, GAMYB genes were consistent with a decrease in starch and increase in soluble sugars levels during dormancy release. Moreover, some genes (ZEP, ABF2, GASA4, GA2OX8) related to ABA and GA metabolism and signal transduction were activated. The relationship between auxin (IAA, IBA, 5-Cl-IAA), and phenolic, including SA levels and dormancy status was also observed.     

Elucidating the role of AlO6‐octahedra in aluminum silicophosphate glasses through topological constraint theory

The local structures of sodium aluminum silicophosphate glasses containing unique AlO₆‐octahedra were characterized through nuclear magnetic resonance (NMR) and modeled by topological constraint theory (TCT). Subsequent calculation results of the glass‐transition temperature (T_g) and Vickers hardness (H_v) obtained using TCT were verified by the experimental data, which provided us evidence of the glass former role of the AlO₆‐octahedra and their behavior in the aluminum‐containing glass systems. The glass‐forming behavior of the AlO₆‐octahedra was identified by their displacement of SiO₆‐octahedra based on their corresponding NMR spectrum. The structure featured a constant total amount of AlO₆ and SiO₆‐octahedra (AlO₆‐octahedra increased whereas SiO₆‐octahedra decreased) with an increasing aluminum content, which was caused by the mutual replacement between them. The glass former role of the AlO₆‐octahedra was further supported by the theoretical computation of T_g and H_v through application of TCT. Specifically, the model of the aluminum‐containing glasses reported here is an extension of the conventional TCT that only incorporates the constraints of the glass formers.     

The Complexation between Amide Groups of Polyamide‐6 and Polysulfides in the Lithium–Sulfur Battery

Lithium–sulfur batteries have attracted considerable attention due to its high theoretical specific capacity, low cost, environmental friendliness, etc. However, the dissolution of polysulfide intermediate in the electrolyte leads to rapid capacity decay in the charge–discharge process. A sulfur‐based cathode with the specific discharge capacity of 630 mAh g⁻¹ and ultrahigh capacity retention ratio of 0.11% per cycle after 400 cycles at 0.5 C that simply blend the sublimed sulfur and acetylene black in the mortar with the polyamide‐6 (PA6) as binder is reported. The intense complexation between the lithium polysulfide and amide groups ( CO NH ) in PA6 can effectively inhibit the “shuttling effect” and reduce the loss of active materials during the charge–discharge process. The discovery provides a handy and practicable strategy for developing the excellent cycling stability lithium–sulfur batteries.

     

Rhodium Acetate Dimer Immobilized in 1‐Butyl‐3‐methylimidazolium Hexafluorophosphate Ionic Liquid: a Novel and Recyclable Catalytic System for the Cyclopropanation of Alkenes

Alkenes undergo smooth cyclopropanation with ethyl diazoacetate using a catalytic amount of rhodium acetate dimer, Rh₂(OAc)₄, immobilized in the air‐ and moisture‐stable 1‐butyl‐3‐methylimidazolium hexafluorophosphate ionic liquid, [bmim]PF₆, to afford cyclopropanecarboxylates in excellent yields with high trans‐selectivity. The recovery of the catalyst is facilitated by the hydrophobic nature of [bmim]PF₆. The recovered ionic liquid containing Rh₂(OAc)₄ can be reused for three to five subsequent runs with only a gradual decrease in activity.