Nature Chemical Biology Contents: September 2015, Volume 11 No 9 pp 619 - 741

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TABLE OF CONTENTS September 2015 Volume 11, Issue 9 Focus Editorial Commentaries Research Highlights News and Views Perspectives Reviews Articles Corrigenda Errata Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement EPIGENOME ROADMAP  Nature Publishing Group presents an online portal -the Epigenome Roadmap - which collects key research papers from The NIH Roadmap Epigenomics Program, complemented by thematical 'threads' to help the readers mine the wealth of available information. Produced with exclusive support from Illumina   Focus Top Focus on Biosynthesis This special issue features Commentaries, Reviews and Perspectives highlighting advances in our understanding of natural product biosynthesis at the chemical, structural, informatic and ecological level, along with new opportunities to create natural product analogues for a variety of applications. Focus on Biosynthesis Editorial Top Looking for logic   p619 doi:10.1038/nchembio.1905 Improved tools and expanding knowledge are enabling new insights into the biochemical basis, ecological roles and promising applications of natural product biosynthesis. Commentaries Top A chemocentric view of the natural product inventory   pp620 - 624 Christopher T Walsh doi:10.1038/nchembio.1894 As the identification of previously undetected microbial biosynthetic pathways burgeons, there arises the question of how much new chemistry is yet to be found. This, in turn, devolves to: what kinds of biosynthetic enzymatic transformations are yet to be characterized? Minimum Information about a Biosynthetic Gene cluster OPEN   pp625 - 631 Marnix H Medema, Renzo Kottmann, Pelin Yilmaz, Matthew Cummings, John B Biggins et al. doi:10.1038/nchembio.1890 A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard. Research Highlights Top Cancer metabolism: Two sides of a coin | Plant microbiota: Root recruiting | Cell cycle regulation: Redox shielding | Biosynthesis: Sniffing out monoterpenes | Proteostasis: Death by cytoplasmic accumulation | Microbiome: Adapting to mucus News and Views Top Protein degradation: Prime time for PROTACs   pp634 - 635 Raymond J Deshaies doi:10.1038/nchembio.1887 PROTACs are heterobifunctional small molecules that simultaneously bind a target protein and a ubiquitin ligase, enabling ubiquitination and degradation of the target. Major progress in developing potent and specific PROTACs has recently been reported, invigorating prospects for novel PROTAC-based therapies. Carbohydrates: A phenol sandwich fights diabetes   pp635 - 636 Anna Bernardi and Sara Sattin doi:10.1038/nchembio.1888 The complex flavonoid montbretin A (MbA) is a powerful inhibitor of human pancreatic amylase (HPA) and a potential tool in the treatment of type 2 diabetes. The X-ray structure of the MbA-HPA complex now shows that a hydrophobic collapse of two phenol fragments in the structure of MbA is key to its activity. See also: Article by Williams et al. Methods: A small-molecule SMASh hit   pp637 - 638 Jeffrey Hannah and Pengbo Zhou doi:10.1038/nchembio.1886 There are many techniques that can be employed to control gene expression at the post-translational level. However, a novel system called SMASh (small molecule-assisted shutoff), which allows for chemically-induced degradation of target proteins, presents some distinct advantages. See also: Article by Chung et al. Chemical Biology JOBS of the week Center for Cell Ultrastructure & Morphology, Director The Scripps Research Institute (TSRI) Postdoctoral Research Assistant University of Oxford Research Laboratory Head / Drug Discovery in Cancer Immunotherapy (m / f) Boehringer Ingelheim Senior Fellow - Parkinson's Disease Research University of Washington Senior Scientist - Tenure Track Paul Scherrer Institut (PSI) More Science jobs from Chemical Biology EVENT The Expanding Toolbox of Medicinal Chemistry: From Chemical Biology to Clinical Applications 16 October 2015 Dijon, France More science events from Perspectives Top Computational approaches to natural product discovery   pp639 - 648 Marnix H Medema and Michael A Fischbach doi:10.1038/nchembio.1884 Reinvigorating natural product combinatorial biosynthesis with synthetic biology   pp649 - 659 Eunji Kim, Bradley S Moore and Yeo Joon Yoon doi:10.1038/nchembio.1893 Reviews Top The structural biology of biosynthetic megaenzymes   pp660 - 670 Kira J Weissman doi:10.1038/nchembio.1883 Translating biosynthetic gene clusters into fungal armor and weaponry   pp671 - 677 Nancy P Keller doi:10.1038/nchembio.1897 Articles Top A new metal binding domain involved in cadmium, cobalt and zinc transport   pp678 - 684 Aaron T Smith, Dulmini Barupala, Timothy L Stemmler and Amy C Rosenzweig doi:10.1038/nchembio.1863 The metal binding domains of P1B-ATPases regulate transport activity via mostly unknown mechanisms. Structural, biochemical and cellular data now describe one such domain that binds two metals using unusual motifs and with different functional consequences. A biosynthetic pathway for a prominent class of microbiota-derived bile acids   pp685 - 690 A Sloan Devlin and Michael A Fischbach doi:10.1038/nchembio.1864 A bioinformatic and phylogenetic search identifies five enzymes involved in the conversion of DCA to isoDCA in the bacterial bile acid biosynthetic pathway. An investigation of the biological roles of bile acids defines a mutualism between the producer R. gnavus and the nonproducer Bacteroides. The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif   pp691 - 696 Leslie K Williams, Xiaohua Zhang, Sami Caner, Christina Tysoe, Nham T Nguyen et al. doi:10.1038/nchembio.1865 Montbretin A is a potent inhibitor of amylase, an enzyme critical in starch digestion and thus of relevance for diabetes and obesity. Structural and biochemical analyses now show that a minimal core of the glycoside π-stacks on itself to fit into the active site. Chemical compounds See also: News and Views by Bernardi & Sattin An excess of catalytically required motions inhibits the scavenger decapping enzyme   pp697 - 704 Ancilla Neu, Ursula Neu, Anna-Lisa Fuchs, Benjamin Schlager and Remco Sprangers doi:10.1038/nchembio.1866 Structural and biochemical studies of scavenger decapping enzyme identify conformational changes induced by substrate binding to a second binding site that occur faster than catalytic turnover, such that high substrate concentrations inhibit enzyme activity. Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms   pp705 - 712 Reiko Ueoka, Agustinus R Uria, Silke Reiter, Tetsushi Mori, Petra Karbaum et al. doi:10.1038/nchembio.1870 Investigations into the biosynthetic pathways of three families of actin-targeting macrolides lead to insights into their convergent or combinatorial evolution, along with the identification of the first free-living bacterial source of macroalga-derived luminaolides. Chemical compounds Tunable and reversible drug control of protein production via a self-excising degron   pp713 - 720 Hokyung K Chung, Conor L Jacobs, Yunwen Huo, Jin Yang, Stefanie A Krumm et al. doi:10.1038/nchembio.1869 SMASh is a strategy for regulating protein stability, in which treatment with a small molecule targets a protein tagged with a self-removing degron that includes an HCV protease sequence. SMASh was used to target measles virus phosphoprotein P, for which no inhibitors exist. See also: News and Views by Hannah & Zhou Analysis of 51 cyclodipeptide synthases reveals the basis for substrate specificity   pp721 - 727 Isabelle B Jacques, Mireille Moutiez, Jerzy Witwinowski, Emmanuelle Darbon, Cecile Martel et al. doi:10.1038/nchembio.1868 Cyclodipeptide synthases use amino acid-loaded tRNAs as substrates to form cyclic peptide dimers. Biochemical and bioinformatic analyses now show that these enzymes are distributed into two phylogenetically distinct major subfamilies and use a broad range of substrates that can be predicted with newly defined sequence motifs. Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy   pp728 - 732 Scott C Farrow, Jillian M Hagel, Guillaume A W Beaudoin, Darcy C Burns and Peter J Facchini doi:10.1038/nchembio.1879 A fusion protein containing P450 and aldo-keto reductase domains is shown to catalyze reticuline isomerization, the critical branch point between the noscapine and morphine biosynthetic pathways. This discovery completes the enzymatic route to morphine and related compounds. A fungal monooxygenase-derived jasmonate attenuates host innate immunity   pp733 - 740 Rajesh N Patkar, Peter I Benke, Ziwei Qu, Yuan Yi Constance Chen, Fan Yang et al. doi:10.1038/nchembio.1885 An antibiotic biosynthesis monooxygenase (Abm) has been identified in the rice blast fungus Magnaporthe oryzae that converts jasmonic acid into hydroxylated JA, which contributes to pathogenicity through the evasion of host immune response. Corrigenda Top Corrigendum: SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice   p741 James Palacino, Susanne E Swalley, Cheng Song, Atwood K Cheung, Lei Shu et al. doi:10.1038/nchembio0915-741a Corrigendum: Sterol metabolism controls TH17 differentiation by generating endogenous RORγ agonists   p741 Xiao Hu, Yahong Wang, Ling-Yang Hao, Xikui Liu, Chuck A Lesch et al. doi:10.1038/nchembio0915-741b Corrigendum: Local and macroscopic electrostatic interactions in single α-helices   p741 Emily G Baker, Gail J Bartlett, Matthew P Crump, Richard B Sessions, Noah Linden et al. doi:10.1038/nchembio0915-741e Errata Top Erratum: Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs   p741 Lingyin Li, Qian Yin, Pia Kuss, Zoltan Maliga, Jose L Millan et al. doi:10.1038/nchembio0915-741c Erratum: Structural basis of enzymatic benzene ring reduction   p741 Tobias Weinert, Simona G Huwiler, Johannes W Kung, Sina Weidenweber, Petra Hellwig et al. doi:10.1038/nchembio0915-741d Top Advertisement Nature Microbiology: Call for Papers Launching in January 2016, Nature Microbiology is now open for submissions and inviting high-quality submissions. 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