Ethylene is important in industry and biological signaling. In plants, ethylene is produced by oxidation of 1-aminocyclopropane-1-carboxylic acid, as catalyzed by 1-aminocyclopropane-1-carboxylic acid oxidase. Bacteria catalyze ethylene production, but via the fourelectron oxidation of 2-oxoglutarate to give ethylene in an argininedependent reaction. Crystallographic and biochemical studies on the Pseudomonas syringae ethylene-forming enzyme reveal a branched mechanism. In one branch, an apparently typical 2-oxoglutarate oxygenase reaction to give succinate, carbon dioxide, and sometimes pyrroline-5-carboxylate occurs. Alternatively, Grob-type oxidative fragmentation of a 2-oxoglutarate-derived intermediate occurs to give ethylene and carbon dioxide. Crystallographic and quantum chemical studies reveal that fragmentation to give ethylene is promoted by binding of L-arginine in a nonoxidized conformation and of 2-oxoglutarate in an unprecedented high-energy conformation that favors ethylene, relative to succinate formation.ethylene-forming enzyme | 2-oxoglutarate-dependent oxygenases | hydroxylase | plant development | oxidoreductase E thylene is of industrial importance and is a vital signaling molecule in plants, where it has roles in germination, senescence, and stress responses (1). Commercial manipulation of the natural ethylene response is agriculturally important in controlling fruit ripening (2). In higher plants, ethylene is produced from methionine, via oxidation of 1-aminocyclopropane-1-carboxylic acid (ACC) in an unusual reaction catalyzed by the Fe(II)-dependent ACC oxidase (ACCO) (3, 4), which is part of the 2-oxoglutarate (2OG)-dependent oxygenase superfamily, although it does not use a 2OG cosubstrate (Fig. 1A) (5-7). Ethylene is also produced in some microorganisms by oxidation of 2-oxo-4-methylthiobutyric acid in a reaction not directly enzyme catalyzed (8,9).In work aimed at producing industrial ethylene by biocatalysis, Pseudomonas strains, including plant pathogens, were shown to produce large amounts of ethylene (10)(11)(12)(13)(14). Bacteria engineered to produce ethylene using the Pseudomonas syringae pv. phaseolicola ethylene-forming enzyme (PsEFE) have been developed to ripen fruit as an alternative to the use of synthetic ethylene (15, 16). Ethylene-forming enzymes are being explored for biocatalysis in cyanobacteria (17-19). PsEFE-catalyzed ethylene production is 2OG-dependent and is stimulated by the addition of L-arginine (L-Arg), which is also converted by PsEFE into pyrroline-5-carboxylate (P5C; Fig. 1B) (13, 20). In contrast to the consensus 2OG oxygenase mechanism, which involves sequential binding of 2OG, substrate, and then oxygen, an unprecedented "dual circuit" mechanism is proposed for PsEFE (13).We describe biochemical, structural, and modeling studies supporting a branched mechanistic pathway for PsEFE that can lead either to ethylene via oxidative fragmentation of 2OG or to succinate via a more typical 2OG oxygenase reaction, which sometimes results in P5C formation (Fig....

Organocatalytic enantioselective desymmetrisation of achiral or meso compounds is a powerful strategy for the construction of enantiomerically enriched complex molecules, often with multiple stereocentres and in high selectivities. Recent years have seen increasing use of organocatalysts in desymmetrisation methodology, in contrast to traditional metal- or enzyme-catalysed reactions, with many impressive advances made in the current decade. This review will provide an overview of the field since 2010, with the aim of highlighting both the practical applications and elegance of enantioselective desymmetrisation to the wider synthetic community.

A mild, catalytic, atom economical synthesis of imidazo[1,2-a]pyridines has been developed: catalytic PicAuCl2 in the presence of an acid produces a range imidazo[1,2-a]pyridines in good yield. This strategy is mild and forseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2-a]pyridine ring without loss of enantiomeric excess.

Rhodium and osmium catalysed C–C and C–O bond formation under mild conditions.

Gold-Catalyzed Redox Synthesis of Imidazo[1,2-a]pyridines Using Pyridine N-Oxide and Alkynes. -The reaction is sensitive to the steric effects and does not tolerate tBu-or mesityl-substituents. Disubstituted alkynes do not produce any desired product. The reaction conditions are applicable to chiral alkynes. -(TALBOT, E. P. A.; RICHARDSON, M.; MCKENNA, J. M.; TOSTE*, F. D.; Adv. Synth. Catal. 356 (2014) 4, 687-691, http://dx.

Review: 247 refs.

ETS2 repressor factor (ERF) insufficiency causes craniosynostosis (CRS4) in humans and mice. ERF is an ETS domain transcriptional repressor regulated by Erk1/2 phosphorylation via nucleo-cytoplasmic shuttling. Here, we analyze the onset and development of the craniosynostosis phenotype in an Erf-insufficient mouse model and evaluate the potential of the residual Erf activity augmented by pharmacological compounds to ameliorate the disease. Erf insufficiency appears to cause an initially compromised frontal bone formation and subsequent multisuture synostosis, reflecting distinct roles of Erf on the cells that give rise to skull and facial bones. We treated animals with Mek1/2 and nuclear export inhibitors, U0126 and KPT-330, respectively, to increase Erf activity by two independent pathways. We implemented both a low dosage locally over the calvaria and a systemic drug administration scheme to evaluate the possible indirect effects from other systems and minimize toxicity. The treatment of mice with either the inhibitors or the administration scheme alleviated the synostosis phenotype with minimal adverse effects. Our data suggest that the ERF level is an important regulator of cranial bone development and that pharmacological modulation of its activity may represent a valid intervention approach both in CRS4 and in other syndromic forms of craniosynostosis mediated by the FGFR-RAS-ERK-ERF pathway.