A new genome-mining tool redefines the lasso peptide biosynthetic landscape

February 28th, 2017 by Jonathan I Tietz

Nature Chemical Biology 13, 470 (2017). doi:10.1038/nchembio.2319

Authors: Jonathan I Tietz, Christopher J Schwalen, Parth S Patel, Tucker Maxson, Patricia M Blair, Hua-Chia Tai, Uzma I Zakai & Douglas A Mitchell

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The Arabidopsis O-fucosyltransferase SPINDLY activates nuclear growth repressor DELLA

February 28th, 2017 by Rodolfo Zentella

Nature Chemical Biology 13, 479 (2017). doi:10.1038/nchembio.2320

Authors: Rodolfo Zentella, Ning Sui, Benjamin Barnhill, Wen-Ping Hsieh, Jianhong Hu, Jeffrey Shabanowitz, Michael Boyce, Neil E Olszewski, Pei Zhou, Donald F Hunt & Tai-ping Sun

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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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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.

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.

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

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.

Accelerating the semisynthesis of alkaloid-based drugs through metabolic engineering

February 15th, 2017 by Amy M Ehrenworth

Nature Chemical Biology 13, 249 (2017). doi:10.1038/nchembio.2308

Authors: Amy M Ehrenworth & Pamela Peralta-Yahya

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mRNA localization: If you have to ASH

February 15th, 2017 by Joshua M. Finkelstein

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2323

Author: Joshua M. Finkelstein

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.