A fully automated flow-based approach for accelerated peptide synthesis
February 28th, 2017 by Alexander J Mijalis
Nature Chemical Biology 13, 464 (2017). doi:10.1038/nchembio.2318
Authors: Alexander J Mijalis, Dale A Thomas, Mark D Simon, Andrea Adamo, Ryan Beaumont, Klavs F Jensen & Bradley L Pentelute
Here we report a fully automated, flow-based approach to solid-phase polypeptide synthesis, with amide bond formation in 7 seconds and total synthesis times of 40 seconds per amino acid residue. Crude peptide purities and isolated yields were comparable to those for standard-batch solid-phase peptide synthesis. At full capacity, this approach can yield tens of thousands of individual 30-mer peptides per year.
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
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.
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.
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.
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
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
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.