CRISPR–Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters

April 10th, 2017 by Mingzi M Zhang

Nature Chemical Biology 13, 607 (2017). doi:10.1038/nchembio.2341

Authors: Mingzi M Zhang, Fong Tian Wong, Yajie Wang, Shangwen Luo, Yee Hwee Lim, Elena Heng, Wan Lin Yeo, Ryan E Cobb, Behnam Enghiad, Ee Lui Ang & Huimin Zhao

Here we report an efficient CRISPR–Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities.

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Mechanistic insights into energy conservation by flavin-based electron bifurcation

April 10th, 2017 by Carolyn E Lubner

Nature Chemical Biology 13, 655 (2017). doi:10.1038/nchembio.2348

Authors: Carolyn E Lubner, David P Jennings, David W Mulder, Gerrit J Schut, Oleg A Zadvornyy, John P Hoben, Monika Tokmina-Lukaszewska, Luke Berry, Diep M Nguyen, Gina L Lipscomb, Brian Bothner, Anne K Jones, Anne-Frances Miller, Paul W King, Michael W W Adams & John W Peters

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Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans

April 3rd, 2017 by Sebastian Boland

Nature Chemical Biology 13, 647 (2017). doi:10.1038/nchembio.2347

Authors: Sebastian Boland, Ulrike Schmidt, Vyacheslav Zagoriy, Julio L Sampaio, Raphael F Fritsche, Regina Czerwonka, Tilo Lübken, Jakob Reimann, Sider Penkov, Hans-Joachim Knölker & Teymuras V Kurzchalia

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AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet

April 3rd, 2017 by Dukas Jurėnas

Nature Chemical Biology 13, 640 (2017). doi:10.1038/nchembio.2346

Authors: Dukas Jurėnas, Sneha Chatterjee, Albert Konijnenberg, Frank Sobott, Louis Droogmans, Abel Garcia-Pino & Laurence Van Melderen

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Insights into activity and inhibition from the crystal structure of human O-GlcNAcase

March 27th, 2017 by Nathaniel L Elsen

Nature Chemical Biology 13, 613 (2017). doi:10.1038/nchembio.2357

Authors: Nathaniel L Elsen, Sangita B Patel, Rachael E Ford, Dawn L Hall, Fred Hess, Hari Kandula, Maria Kornienko, John Reid, Harold Selnick, Jennifer M Shipman, Sujata Sharma, Kevin J Lumb, Stephen M Soisson & Daniel J Klein

O-GlcNAc hydrolase (OGA) catalyzes removal of βα-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain α-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities.

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Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase

March 27th, 2017 by Stephanie M Stanford

Nature Chemical Biology 13, 624 (2017). doi:10.1038/nchembio.2344

Authors: Stephanie M Stanford, Alexander E Aleshin, Vida Zhang, Robert J Ardecky, Michael P Hedrick, Jiwen Zou, Santhi R Ganji, Matthew R Bliss, Fusayo Yamamoto, Andrey A Bobkov, Janna Kiselar, Yingge Liu, Gregory W Cadwell, Shilpi Khare, Jinghua Yu, Antonio Barquilla, Thomas D Y Chung, Tomas Mustelin, Simon Schenk, Laurie A Bankston, Robert C Liddington, Anthony B Pinkerton & Nunzio Bottini

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Chemical screening identifies ATM as a target for alleviating senescence

March 27th, 2017 by Hyun Tae Kang

Nature Chemical Biology 13, 616 (2017). doi:10.1038/nchembio.2342

Authors: Hyun Tae Kang, Joon Tae Park, Kobong Choi, Yongsub Kim, Hyo Jei Claudia Choi, Chul Won Jung, Young-Sam Lee & Sang Chul Park

  • Posted in Nat Chem Biol, Publications
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Near-infrared optogenetic pair for protein regulation and spectral multiplexing

March 27th, 2017 by Taras A Redchuk

Nature Chemical Biology 13, 633 (2017). doi:10.1038/nchembio.2343

Authors: Taras A Redchuk, Evgeniya S Omelina, Konstantin G Chernov & Vladislav V Verkhusha

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Structural and functional insight into human O-GlcNAcase

March 27th, 2017 by Christian Roth

Nature Chemical Biology 13, 610 (2017). doi:10.1038/nchembio.2358

Authors: Christian Roth, Sherry Chan, Wendy A Offen, Glyn R Hemsworth, Lianne I Willems, Dustin T King, Vimal Varghese, Robert Britton, David J Vocadlo & Gideon J Davies

O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.

Fatty acid synthases: Re-engineering biofactories

March 22nd, 2017 by Timm Maier

Nature Chemical Biology 13, 344 (2017). doi:10.1038/nchembio.2338

Author: Timm Maier

Systematically modifying biological assembly lines for the synthesis of novel products remains a challenge. Structural insights and computational modeling have now paved the way for efficient redesigns of giant fatty acid synthases.