Naoko Ichiishi

Plan would slash nonmilitary spending for remainder of fiscal 2017

Nature Chemistry. doi:10.1038/nchem.2714

Authors: Alhosna Benjdia, Alain Guillot, Pauline Ruffié, Jérôme Leprince & Olivier Berteau

Radical SAM enzymes are versatile enzymes catalysing chemically challenging reactions. Now, a radical SAM enzyme that post-translationally modifies ribosomally synthesized peptides to contain D-amino acids has been discovered in Bacillus subtilis, and its mechanism has been deciphered. These peptides, called epipeptides, efficiently inhibit bacterial growth.

Nature Chemistry. doi:10.1038/nchem.2741

Authors: Kevin Wu & Abigail G. Doyle

Ligand development underlies many advances in Pd-catalysed cross coupling but has seen limited application in the growing field of Ni catalysis. Now, a phosphine framework is shown to enable Ni-catalysed Suzuki coupling of acetals. Parameterization studies provide structural insight into ligand success and a quantitative model to facilitate further ligand design.

Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites. Authors: Enrique Marcos, Benjamin Basanta, Tamuka M. Chidyausiku, Yuefeng Tang, Gustav Oberdorfer, Gaohua Liu, G. V. T. Swapna, Rongjin Guan, Daniel-Adriano Silva, Jiayi Dou, Jose Henrique Pereira, Rong Xiao, Banumathi Sankaran, Peter H. Zwart, Gaetano T. Montelione, David Baker

Nature Chemistry. doi:10.1038/nchem.2690

Authors: Hyowon Seo, Matthew H. Katcher & Timothy F. Jamison

Although the synthetic chemistry of carbon dioxide has generally been limited to two-electron pathways, single-electron mechanisms would open avenues to new reactivity. Now, the coupling of carbon dioxide and amines to produce α-amino acids can be achieved by an organic photoredox catalyst in continuous flow.

Nature Chemistry. doi:10.1038/nchem.2697

Authors: Jamie H. Docherty, Jingying Peng, Andrew P. Dominey & Stephen P. Thomas

NaOtBu — an alkoxide salt — enables simple access to low-oxidation-state catalysis using sustainable first-row transition metals (Fe, Co, Mn, Ni). The approach works across a wide range of reductive alkene and alkyne functionlization reactions including hydroboration, hydrosilylation, hydrogenation, hydrovinylation and [2π+2π] cyclization reactions.

Organometallic chemist honored for his efforts to activate carbon-hydrogen bonds

The human genome produces thousands of long noncoding RNAs (lncRNAs)—transcripts >200 nucleotides long that do not encode proteins. Although critical roles in normal biology and disease have been revealed for a subset of lncRNAs, the function of the vast majority remains untested. We developed a CRISPR interference (CRISPRi) platform targeting 16,401 lncRNA loci in seven diverse cell lines, including six transformed cell lines and human induced pluripotent stem cells (iPSCs). Large-scale screening identified 499 lncRNA loci required for robust cellular growth, of which 89% showed growth-modifying function exclusively in one cell type. We further found that lncRNA knockdown can perturb complex transcriptional networks in a cell type–specific manner. These data underscore the functional importance and cell type specificity of many lncRNAs. Authors: S. John Liu, Max A. Horlbeck, Seung Woo Cho, Harjus S. Birk, Martina Malatesta, Daniel He, Frank J. Attenello, Jacqueline E. Villalta, Min Y. Cho, Yuwen Chen, Mohammad A. Mandegar, Michael P. Olvera, Luke A. Gilbert, Bruce R. Conklin, Howard Y. Chang, Jonathan S. Weissman, Daniel A. Lim

Nature Chemistry. doi:10.1038/nchem.2677

Authors: Haining Wang, Xi-Jie Dai & Chao-Jun Li

Methods utilizing renewable feedstocks are critical to accessing molecules of industrial importance in light of the present ecological and economic climate. Here, it is shown that umpolung reactivity of carbonyl compounds can be used for nucleophilic additions to yield a diverse array of valuable alcohols as an alternative to using stoichiometric organometallic reagents.

Nature Chemistry. doi:10.1038/nchem.2671

Authors: Xiaofeng Cai, Sarah Nowak, Frank Wesche, Iris Bischoff, Marcel Kaiser, Robert Fürst & Helge. B. Bode

Nature has evolved a variety of different mechanisms to generate chemical diversity, however the reactions responsible for generating such diverse chemical libraries are often not clear. Now, the mechanisms employed by entomopathogenic bacteria for the biosynthesis of a large family of bioactive peptides have been identified. These include substrate promiscuity, enzyme cross-talk and enzyme stoichiometry.