Nature Chemical Biology Contents: August 2013 Volume 9 Number 8 pp 468 - 526

TABLE OF CONTENTS August 2013 Volume 9, Issue 8 Research Highlights News and Views Review Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Unleash your ideas and win cash awards! Innovative solutions to scientific Challenges on the nature.com Open Innovation Pavilion have resulted in over $1.5 million in cash prizes to Solvers. Challenges are available in all areas of science and do not require the Solver to have a specific area of expertise or educational degree. Registration to the Pavilion is free.   Research Highlights Top Metabolic engineering: Polyphenols on order | Molecular recognition: Mimicry origins | X-inactivation: RNA eviction notice | Drug resistance: Starving for ATP | Biosynthesis: Deciphering dehydrophos | Cancer: High fat deals a low blow | Photoswitches: Ready for red | Neuroscience: Along came a long RNA News and Views Top Protein engineering: Chemistry gets the assist   pp470 - 471 Bettina M Nestl and Bernhard Hauer doi:10.1038/nchembio.1291 Integration of chemistry-based approaches into enzyme engineering provides a versatile strategy for biocatalyst development with the potential for improved performance and new catalytic activities. Application of this strategy led to the development of a whole-cell catalyst capable of converting olefins into cyclopropanes, synthetic intermediates used in the synthesis of more functionalized cycloalkanes and acyclic compounds. See also: Brief Communication by Coelho et al. Metabolomics: Playing pinata with single cells   pp471 - 473 Oscar Yanes doi:10.1038/nchembio.1297 Mass spectrometry advances in single-cell metabolomics enable the discovery of a new biological insight that is not accessible from population-level studies. A new study reveals that single baker's yeast cells provide sufficient material to study chemical and genetic inhibition of glycolysis and identifies metabolic subpopulations that would be invisible in bulk. Channels: Sticking to nooks and crannies   pp473 - 474 Heike Wulff and Vladimir Yarov-Yarovoy doi:10.1038/nchembio.1292 Drug design for voltage-gated ion channels has long been hampered by the absence of crystal structures and the challenge of achieving subtype selectivity. A combination of mutagenesis, electrophysiology and molecular modeling has led to the identification of a new side pocket binding site for the small molecule Psora-4 between the pore and the voltage-sensor domain of Kv1.5, offering opportunities to design allosteric ion channel modulators. See also: Article by Marzian et al. Chemical Biology JOBS of the week PhD Studentship in Bio-inspired Nanosensors University of Southampton PhD student position in metabolic and process engineering Chalmers University of Technology Department Director The Max Planck Institute of Molecular Physiology (MPI-MP) PhD position in Vascular Biology University Medical Center Hamburg-Eppendorf, Germany Institute Assoc Scientist III - Molecular Biology MD Anderson Cancer Center More Science jobs from Review Top Chemical reporters for biological discovery   pp475 - 484 Markus Grammel and Howard C Hang doi:10.1038/nchembio.1296 Bioorthogonal chemistry, facilitated by enzymatic incorporation of chemical reporters in vitro or in cells, permits selective labeling and visualization of proteins, nucleic acids and other biomolecules such as glycans and lipids and facilitates the interrogation of their cellular functions. Brief Communications Top A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo    pp485 - 487 Pedro S Coelho, Z Jane Wang, Maraia E Ener, Stefanie A Baril and Arvind Kannan et al. doi:10.1038/nchembio.1278 The exchange of a heme-ligating cysteine for a serine residue in an engineered P450 alters the redox potential of the enzyme, deactivating wild-type function and enabling efficient, NADPH-mediated carbene transfer in cells. See also: News and Views by Nestl & Hauer Observation of a stable carbene at the active site of a thiamin enzyme   pp488 - 490 Danilo Meyer, Piotr Neumann, Ralf Ficner and Kai Tittmann doi:10.1038/nchembio.1275 Carbenes have been postulated to take part in the catalytic cycle of several enzymes, but direct detection of these unstable compounds has been elusive. Spectroscopic and structural studies of pyruvate oxidase now identify a carbene-containing cofactor, calling for reinspection of existing enzyme mechanisms. A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis   pp491 - 493 Jonathan Gisin, Alexander Schneider, Bettina Nägele, Marina Borisova and Christoph Mayer doi:10.1038/nchembio.1289 Fosfomycin inhibits cell wall formation by preventing MurA-mediated UDP-MurNAc synthesis, but resistance to this drug suggested another route to UDP-MurNAc might exist. Genetic and biochemical studies identify two genes that, with an unknown phosphatase, define a new MurNAc salvage pathway. Articles Top Evolution of a designed retro-aldolase leads to complete active site remodeling   pp494 - 498 Lars Giger, Sami Caner, Richard Obexer, Peter Kast and David Baker et al. doi:10.1038/nchembio.1276 A previously designed enzyme used a reactive lysine to initiate cleavage of a carbon-carbon bond. Directed evolution of this construct now shows a drastic reorganization of the active site to use an alternative catalytic lysine and suggests considerations for future design efforts. Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis   pp499 - 506 Regina Wilson, Pradeep Kumar, Vijay Parashar, Catherine Vilchèze and Romain Veyron-Churlet et al. doi:10.1038/nchembio.1277 Thiophene compounds kill M. tuberculosis by inhibiting Pks13, demonstrating that the enzyme catalyzes a critical step in biosynthesis of mycolic acids in vivo. Chemical compounds Side pockets provide the basis for a new mechanism of Kv channel–specific inhibition   pp507 - 513 Stefanie Marzian, Phillip J Stansfeld, Markus Rapedius, Susanne Rinné and Ehsan Nematian-Ardestani et al. doi:10.1038/nchembio.1271 A Kv1 channel inhibitor and potential therapeutic lead achieves selectivity by binding both the conserved central cavity and newly identified side pockets, which provide the key determinants for channel specificity. See also: Article by Marzian et al. Identification of small molecules for human hepatocyte expansion and iPS differentiation   pp514 - 520 Jing Shan, Robert E Schwartz, Nathan T Ross, David J Logan and David Thomas et al. doi:10.1038/nchembio.1270 A high-throughput chemical screen of primary human hepatocytes in combination with machine-learning algorithms for evaluation of imaging data identifies compounds that promote expansion of primary human hepatocytes and maturation from human iPS cells toward an adult-like hepatocyte phenotype. Chemical compounds Synthetic glycopeptides reveal the glycan specificity of HIV-neutralizing antibodies   pp521 - 526 Mohammed N Amin, Jason S McLellan, Wei Huang, Jared Orwenyo and Dennis R Burton et al. doi:10.1038/nchembio.1288 Chemoenzymatic synthesis of glycopeptides enables the identification of glycan specificity of two broadly neutralizing antibodies against HIV-1. 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