Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products are attractive for genome-driven discovery and re-engineering, but limitations in bioinformatic methods and exponentially increasing genomic data make large-scale mining difficult. We report RODEO (Rapid ORF Description and Evaluation Online), which combines hidden Markov model-based analysis, heuristic scoring, and machine learning to identify biosynthetic gene clusters and predict RiPP precursor peptides. We initially focused on lasso peptides, which display intriguing physiochemical properties and bioactivities, but their hypervariability renders them challenging prospects for automated mining. Our approach yielded the most comprehensive mapping of lasso peptide space, revealing >1,300 compounds. We characterized the structures and bioactivities of six lasso peptides, prioritized based on predicted structural novelty, including an unprecedented handcuff-like topology and another with a citrulline modification exceptionally rare among bacteria. These combined insights significantly expand the knowledge of lasso peptides, and more broadly, provide a framework for future genome-mining efforts.

Extended investigation of electrocatalytic generation of dihydrogen using [(mu-1,2-benzenedithiolato)][Fe(CO)3]2 has revealed that weak acids, such as acetic acid, can be used. The catalytic reduction producing dihydrogen occurs at approximately -2 V for several carboxylic acids and phenols resulting in overpotentials of only -0.44 to -0.71 V depending on the weak acid used. This unusual catalytic reduction occurs at a potential at which the starting material, in the absence of a proton source, does not show a reduction peak. The mechanism for this process and structures for the intermediates have been discerned by electrochemical and computational analysis. These studies reveal that the catalyst is the monoanion of the starting material and an ECEC mechanism occurs.

Tricin was recently discovered in lignin preparations from wheat (Triticum aestivum) straw and subsequently in all monocot samples examined. To provide proof that tricin is involved in lignification and establish the mechanism by which it incorporates into the lignin polymer, the 49-Ob-coupling products of tricin with the monolignols (p-coumaryl, coniferyl, and sinapyl alcohols) were synthesized along with the trimer that would result from its 49-O-b-coupling with sinapyl alcohol and then coniferyl alcohol. Tricin was also found to cross couple with monolignols to form tricin-(49-O-b)-linked dimers in biomimetic oxidations using peroxidase/hydrogen peroxide or silver (I) oxide. Nuclear magnetic resonance characterization of gel permeation chromatography-fractionated acetylated maize (Zea mays) lignin revealed that the tricin moieties are found in even the highest molecular weight fractions, ether linked to lignin units, demonstrating that tricin is indeed incorporated into the lignin polymer. These findings suggest that tricin is fully compatible with lignification reactions, is an authentic lignin monomer, and, because it can only start a lignin chain, functions as a nucleation site for lignification in monocots. This initiation role helps resolve a long-standing dilemma that monocot lignin chains do not appear to be initiated by monolignol homodehydrodimerization as they are in dicots that have similar syringyl-guaiacyl compositions. The term flavonolignin is recommended for the racemic oligomers and polymers of monolignols that start from tricin (or incorporate other flavonoids) in the cell wall, in analogy with the existing term flavonolignan that is used for the lowmolecular mass compounds composed of flavonoid and lignan moieties.Lignin, a complex phenylpropanoid polymer in the plant cell wall, is predominantly deposited in the cell walls of secondary-thickened cells (Vanholme et al., 2010). It is synthesized via oxidative radical coupling reactions from three prototypical monolignols, p-coumaryl, coniferyl, and sinapyl alcohols, differentiated by their degree of methoxylation ortho to the phenolic hydroxyl group. Considered within the context of the entire polymer, the main structural features of lignin can be defined in terms of its p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) units, derived respectively from these three monolignols (Ralph, 2010). Several novel monomers, all deriving from the monolignol biosynthetic pathway, have been found to incorporate into lignin in wild-type and transgenic plants. For example, monolignol acetate, p-hydroxybenzoate, and p-coumarate ester conjugates have all been shown to incorporate into lignin polymers and are the source of naturally acylated lignins (Ralph et al., 2004;Lu and Ralph, 2008); lignins derived solely from caffeyl alcohol were found in the seed coats of both monocot and dicot plants (Chen et al., 2012a(Chen et al., , 2012b; lignins derived solely from 5-hydroxyconiferyl alcohol were found in a cactus (for example, in a member of the genera Astrop...

Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions.

Using phenolic bio‐oil as feedstock for sustainable production of alkane fuels is of great significance. Here, the hydrodeoxygenation of phenol and its derivatives has been systematically investigated in aqueous media with a dual‐functional catalyst system consisting of water‐soluble, ionic liquid‐like copolymer A‐stabilized nanocatalysts and the mineral acid H3PO4. The developed Ru/A‐H3PO4 catalyst system achieved a complete phenol conversion with cyclohexane selectivity higher than 99 %, making it by far one of the most efficient systems for phenol hydrodeoxygenation. Mercury poisoning experiments revealed that the in situ generated Ru nanoparticles are true a heterogeneous catalyst for hydrogenation. The catalytic activity of metal site for phenol hydrodeoxygenation to cyclohexane decreased with the order of Ru>Rh>Pt≫Pd. Our findings also demonstrated the delicate balance between activity and stability of ionic liquid‐like copolymer‐stabilized nanocatalysts. The research highlights an efficient catalyst system of transforming phenols into alkanes.

The diverse electrochemical and chemical oxidations of dichalcogena-mesocycles are analyzed, broadening our understanding of the chemistry of the corresponding radical cations and dications. 1,5-Diselenocane and 1,5-ditellurocane undergo reversible two-electron oxidation with inverted potentials analogous to 1,5-dithiocane. On the other hand, 1,5-selenathiocane and 1,5-tellurathiocane undergo one-electron oxidative dimerization. The X-ray crystal structures of the Se-Se dimer of the 1,5-selenathiocane one-electron oxidized product and the monomeric two-electron oxidized product (dication) of 1,5-tellurathiocane are reported. 1,5-Dithiocanes and 1,5-diselenocanes with group 14 atoms as ring members undergo irreversible oxidation, unlike the reversible two-electron oxidation of the corresponding silicon-containing 1,5-ditellurocanes. These results demonstrate the chemical consequences of the dication stabilities Te(+)-Te(+) > Se(+)-Se(+) > S(+)-S(+), as well as Se(+)-Se(+) > Se(+)-S(+) and Te(+)-Te(+) > Te(+)-S(+).

Stannylated dinuclear iron dithiolates (mu-SSnMe(2)CH(2)S)[Fe(CO)(3)](2), (mu-SCH(2)SnMe(2)CH(2)S) [Fe(CO)(3)](2), and (mu-SCH(2)SnMe(3))(2)[Fe(CO)(3)](2), which are structurally similar to the active site of iron-only hydrogenase, were synthesized and studied by gas-phase photoelectron spectroscopy. The orbital origins of ionizations were assigned by comparison of He I and He II photoelectron spectra and with the aid of hybrid density functional electronic structure calculations. Stannylation lowers the ionization energy of sulfur lone pair orbitals in these systems owing to a geometry-dependent interaction. The Fe-Fe sigma bond, which is the HOMO in all these systems, is also substantially destabilized by stannylation due to a previously unrecognized geometry-dependent interaction between axial sulfur lone pair orbitals and the Fe-Fe sigma bond. Since cleaving the Fe-Fe sigma bond is a key step in the mechanism of action of iron-only hydrogenase, these newly recognized geometry-dependent interactions may be utilized in designing biologically inspired hydrogenase catalysts.

Several 1,3-diphenyl-substituted silafluorene compounds were synthesized and characterized as potential fluorescent materials for OLED fabrication and bioimaging. Introducing phenyl groups into the silafluorene ring at the 1and 3-positions led to a red shift in the emission, resulting in blue light emitting compounds (λ max 368−375 nm in solution; λ max 362−371 and 482 nm in the solid state), and improved the quantum yield efficiency both in solution and as solids. Aggregation enhanced emission of the silafluorenes (AEE) was also investigated. Theoretical MO calculations were carried out to aid in understanding the optical properties of these molecules. Since these compounds might be useful in bioimaging, their toxicity was also investigated in skin fibroblast cells. All compounds were found to be nontoxic to the investigated cell cultures.