Nature Chemical Biology 5, 863 (2009). doi:10.1038/nchembio.272

The third Nature Chemical Biology symposium brought together nearly 200 scientists to explore the frontiers of chemical biology and drug discovery.

Nature Chemical Biology 5, 865 (2009). doi:10.1038/nchembio.260

Authors: Jon O Lundberg, Mark T Gladwin, Amrita Ahluwalia, Nigel Benjamin, Nathan S Bryan, Anthony Butler, Pedro Cabrales, Angela Fago, Martin Feelisch, Peter C Ford, Bruce A Freeman, Michael Frenneaux, Joel Friedman, Malte Kelm, Christopher G Kevil, Daniel B Kim-Shapiro, Andrey V Kozlov, Jack R Lancaster, David J Lefer, Kenneth McColl, Kenneth McCurry, Rakesh P Patel, Joel Petersson, Tienush Rassaf, Valentin P Reutov, George B Richter-Addo, Alan Schechter, Sruti Shiva, Koichiro Tsuchiya, Ernst E van Faassen, Andrew J Webb, Brian S Zuckerbraun, Jay L Zweier & Eddie Weitzberg

Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.

Nature Chemical Biology 5, 870 (2009). doi:10.1038/nchembio.263

Author: Vanessa Sperandio

Vibrio cholerae produces cholera autoinducer-1 (CAI-1), a signaling molecule previously believed to be synthesized by the CqsA enzyme. Here it is shown that CqsA does not directly synthesize CAI-1; instead, it synthesizes amino-CAI-1, which is then converted into CAI-1 in a CqsA-independent manner.

Nature Chemical Biology 5, 871 (2009). doi:10.1038/nchembio.267

Author: Andrei L Osterman

A unique heterotrimeric assembly of individually inactive paralogs, two of which are also involved in regulating phosphatase activity, creates one of the key enzymes of coenzyme A biosynthesis in yeast, pointing to the possibility of a previously undescribed cross-talk between metabolic and signaling pathways.

Nature Chemical Biology 5, 873 (2009). doi:10.1038/nchembio.262

Authors: Rebecca Toroney & Philip C Bevilacqua

The RNA-activated protein kinase PKR inhibits translation initiation by sensing long viral double-stranded RNA. A new report indicates that PKR is also activated by a cellular mRNA, but only when ribosomes are not initiating translation.

Nature Chemical Biology 5, 874 (2009). doi:10.1038/nchembio.261

Authors: Naoko Takahashi-Makise, Diane McVey Ward & Jerry Kaplan

Two iron regulatory proteins (IRP1 and IRP2) regulate translation and/or stability of mRNAs encoding proteins required for iron storage, acquisition and utilization. Rather than IRP2 directly sensing iron concentrations, iron has been shown to regulate the level of the SKP1-CUL1-FBXL5 E3 ubiquitin ligase protein complex, which is responsible for IRP2 degradation.

LC/MS analysis of cellular RNA reveals NAD-linked RNA

Nature Chemical Biology 5, 879 (2009). doi:10.1038/nchembio.235

Authors: Y Grace Chen, Walter E Kowtoniuk, Isha Agarwal, Yinghua Shen & David R Liu

We developed a general method to detect cellular small molecule–RNA conjugates that does not rely on the reactivity of the small molecule. This technique revealed NAD-linked RNA in Escherichia coli and Streptomyces venezuelae. Subsequent characterization showed that NAD is a 5′ modification of RNA, cannot be installed in vitro through aberrant transcriptional initiation, is only found among smaller cellular RNAs and is present at a surprisingly high abundance of ∼3,000 copies per cell.

An artificial di-iron oxo-protein with phenol oxidase activity

Nature Chemical Biology 5, 882 (2009). doi:10.1038/nchembio.257

Authors: Marina Faiella, Concetta Andreozzi, Rafael Torres Martin de Rosales, Vincenzo Pavone, Ornella Maglio, Flavia Nastri, William F DeGrado & Angela Lombardi

Here we report the de novo design and NMR structure of a four-helical bundle di-iron protein with phenol oxidase activity. The introduction of the cofactor-binding and phenol-binding sites required the incorporation of residues that were detrimental to the free energy of folding of the protein. Sufficient stability was, however, obtained by optimizing the sequence of a loop distant from the active site.

Translating metabolic exchange with imaging mass spectrometry

Nature Chemical Biology 5, 885 (2009). doi:10.1038/nchembio.252

Authors: Yu-Liang Yang, Yuquan Xu, Paul Straight & Pieter C Dorrestein

Metabolic exchange between an organism and the environment, including interactions with neighboring organisms, is important for processes of organismal development. Here we develop and use thin-layer agar natural product MALDI-TOF imaging mass spectrometry of intact bacterial colonies grown on top of the MALDI target plate to study an interaction between two species of bacteria and provide direct evidence that Bacillus subtilis silences the defensive arsenal of Streptomyces coelicolor.

Diverse backbone-cyclized peptides via codon reprogramming

Nature Chemical Biology 5, 888 (2009). doi:10.1038/nchembio.259

Authors: Takashi Kawakami, Atsushi Ohta, Masaki Ohuchi, Hiroshi Ashigai, Hiroshi Murakami & Hiroaki Suga

We report a methodology for the ribosomal synthesis of backbone-cyclized peptides involving genetic code reprogramming to introduce one or more nonproteinogenic amino acids. Expression of linear peptides bearing a cysteine-proline dipeptide sequence followed by glycolic acid results in self-rearrangement to a C-terminal diketopiperadine-thioester, which non-enzymatically generates a cyclized peptide. We demonstrate the ribosomal synthesis of several naturally occurring backbone-cyclized peptides and a library based on a bicyclic scaffold, and we identify bioactive sequences by screening and deconvolution.