Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11

February 28th, 2017 by Jing Li

Nature Chemical Biology 13, 486 (2017). doi:10.1038/nchembio.2326

Authors: Jing Li, Tanya Yakushi, Francesco Parlati, Andrew L Mackinnon, Christian Perez, Yuyong Ma, Kyle P Carter, Sharon Colayco, Gavin Magnuson, Brock Brown, Kevin Nguyen, Stefan Vasile, Eigo Suyama, Layton H Smith, Eduard Sergienko, Anthony B Pinkerton, Thomas D Y Chung, Amy E Palmer, Ian Pass, Sonja Hess, Seth M Cohen & Raymond J Deshaies

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Synthetic Riboswitches: From Plug and Pray toward Plug and Play

February 24th, 2017 by Maja Etzel and Mario Mòˆrl

TOC Graphic

DOI: 10.1021/acs.biochem.6b01218

Ligand-promoted protein folding by biased kinetic partitioning

February 20th, 2017 by Karan S Hingorani

Nature Chemical Biology 13, 369 (2017). doi:10.1038/nchembio.2303

Authors: Karan S Hingorani, Matthew C Metcalf, Derrick T Deming, Scott C Garman, Evan T Powers & Lila M Gierasch

Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.

Engineering fatty acid synthases for directed polyketide production

February 20th, 2017 by Jan Gajewski

Nature Chemical Biology 13, 363 (2017). doi:10.1038/nchembio.2314

Authors: Jan Gajewski, Floris Buelens, Sascha Serdjukow, Melanie Janßen, Niña Cortina, Helmut Grubmüller & Martin Grininger

In this study, we engineered fatty acid synthases (FAS) for the biosynthesis of short-chain fatty acids and polyketides, guided by a combined in vitro and in silico approach. Along with exploring the synthetic capability of FAS, we aim to build a foundation for efficient protein engineering, with the specific goal of harnessing evolutionarily related megadalton-scale polyketide synthases (PKS) for the tailored production of bioactive natural compounds.

Expanding the product portfolio of fungal type I fatty acid synthases

February 20th, 2017 by Zhiwei Zhu

Nature Chemical Biology 13, 360 (2017). doi:10.1038/nchembio.2301

Authors: Zhiwei Zhu, Yongjin J Zhou, Anastasia Krivoruchko, Martin Grininger, Zongbao K Zhao & Jens Nielsen

Fungal type I fatty acid synthases (FASs) are mega-enzymes with two separated, identical compartments, in which the acyl carrier protein (ACP) domains shuttle substrates to catalytically active sites embedded in the chamber wall. We devised synthetic FASs by integrating heterologous enzymes into the reaction chambers and demonstrated their capability to convert acyl-ACP or acyl-CoA from canonical fatty acid biosynthesis to short/medium-chain fatty acids and methyl ketones.

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G-Protein-coupled receptors: Decoding mixed signals

February 15th, 2017 by Thomas J Gardella

Nature Chemical Biology 13, 247 (2017). doi:10.1038/nchembio.2316

Author: Thomas J Gardella

A new mechanism of functional crosstalk between two distinct G-protein-coupled receptors (GPCRs)—the parathyroid hormone receptor (PTHR) and β2-adrenergic receptor (β2 Ar)—that occurs at the level of G protein βγ subunits and a specific adenylyl cyclase isoform is identified. This crosstalk augments cAMP signaling by the PTHR from endosomes, and thus promotes the actions of PTH ligands in bone target cells.

Metabolism: A-way with biofilms

February 15th, 2017 by Mirella Bucci

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2325

Author: Mirella Bucci

Plant infection: A decoy tactic

February 15th, 2017 by Grant Miura

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2322

Author: Grant Miura

Enzyme mechanisms: Fickle about fluorine

February 15th, 2017 by Caitlin Deane

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2324

Author: Caitlin Deane

Synthetic biology: Synthetic gene networks that smell

February 15th, 2017 by Fahim Farzadfard

Nature Chemical Biology 13, 245 (2017). doi:10.1038/nchembio.2315

Authors: Fahim Farzadfard & Timothy K Lu

Bioengineers have endowed a consortium of human cells with an artificial sense of smell, enabling the cells to detect, quantify, and remember the presence of gaseous volatile compounds in their environment.