A nitrous acid biosynthetic pathway for diazo group formation in bacteria

December 21st, 2015 by Yoshinori Sugai

Nature Chemical Biology 12, 73 (2016). doi:10.1038/nchembio.1991

Authors: Yoshinori Sugai, Yohei Katsuyama & Yasuo Ohnishi

Although some diazo compounds have bioactivities of medicinal interest, little is known about diazo group formation in nature. Here we describe an unprecedented nitrous acid biosynthetic pathway responsible for the formation of a diazo group in the biosynthesis of the ortho-diazoquinone secondary metabolite cremeomycin in Streptomyces cremeus. This finding provides important insights into the biosynthetic pathways not only for diazo compounds but also for other naturally occurring compounds containing nitrogen-nitrogen bonds.

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Cancer therapy: Vitamin C attack

December 17th, 2015 by Grant Miura

Nature Chemical Biology 12, 1 (2016). doi:10.1038/nchembio.1995

Author: Grant Miura

Pharmacological chaperones: A new lens on cataract

December 17th, 2015 by Mirella Bucci

Nature Chemical Biology 12, 1 (2016). doi:10.1038/nchembio.1993

Author: Mirella Bucci

Probe discovery: Disentangling gene networks

December 17th, 2015 by Finbarr Hayes

Nature Chemical Biology 12, 3 (2016). doi:10.1038/nchembio.1983

Author: Finbarr Hayes

Cell-wall biogenesis in bacteria involves multiple intersecting gene networks. A powerful approach that allies synthetic lethality with small-molecule discovery has now been used to probe these networks and has revealed that the pathway for D-alanylation of teichoic acids in Staphylococcus aureus is a viable target for new antibacterials.

Microscopy techniques: A localization module

December 17th, 2015 by Mirella Bucci

Nature Chemical Biology 12, 1 (2016). doi:10.1038/nchembio.1994

Author: Mirella Bucci

Protein Design: Getting to the bottom of the TIM barrel

December 17th, 2015 by Vikas Nanda

Nature Chemical Biology 12, 2 (2016). doi:10.1038/nchembio.1987

Author: Vikas Nanda

Natural (βα)8-barrel proteins support diverse catalytic functions and are fertile scaffolds for engineering synthetic enzymes. The atomic-resolution structure determination of a computationally guided, de novo–designed symmetric barrel is a long-awaited advance that opens up new opportunities for enzyme design.

Transcriptional kinases: Less is more (or less)

December 17th, 2015 by Thomas G Boyer

Nature Chemical Biology 12, 4 (2016). doi:10.1038/nchembio.1985

Author: Thomas G Boyer

Two new studies describe potent and selective inhibitors of CDK8/CDK19. Application of these high-quality probes to several cancer models provides new mechanistic insight and reveals functional dichotomy with respect to Mediator kinases in signal-dependent gene regulation, with important implications for targeted cancer therapy.

Antibacterials: Stressing out dormancy

December 17th, 2015 by Grant Miura

Nature Chemical Biology 12, 1 (2016). doi:10.1038/nchembio.1992

Author: Grant Miura

Correlating chemical sensitivity and basal gene expression reveals mechanism of action

December 14th, 2015 by Matthew G Rees

Nature Chemical Biology 12, 109 (2016). doi:10.1038/nchembio.1986

Authors: Matthew G Rees, Brinton Seashore-Ludlow, Jaime H Cheah, Drew J Adams, Edmund V Price, Shubhroz Gill, Sarah Javaid, Matthew E Coletti, Victor L Jones, Nicole E Bodycombe, Christian K Soule, Benjamin Alexander, Ava Li, Philip Montgomery, Joanne D Kotz, C Suk-Yee Hon, Benito Munoz, Ted Liefeld, Vlado Dančík, Daniel A Haber, Clary B Clish, Joshua A Bittker, Michelle Palmer, Bridget K Wagner, Paul A Clemons, Alykhan F Shamji & Stuart L Schreiber

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Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics

December 14th, 2015 by Luc de Waal

Nature Chemical Biology 12, 102 (2016). doi:10.1038/nchembio.1984

Authors: Luc de Waal, Timothy A Lewis, Matthew G Rees, Aviad Tsherniak, Xiaoyun Wu, Peter S Choi, Lara Gechijian, Christina Hartigan, Patrick W Faloon, Mark J Hickey, Nicola Tolliday, Steven A Carr, Paul A Clemons, Benito Munoz, Bridget K Wagner, Alykhan F Shamji, Angela N Koehler, Monica Schenone, Alex B Burgin, Stuart L Schreiber, Heidi Greulich & Matthew Meyerson

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