Chemical biology articles within Nature

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• Article | 30 October 2019

  Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds

  Compounds that interact with mutant huntingtin and an autophagosomal protein are able to reduce cellular levels of mutant huntingtin by targeting it for autophagic degradation, demonstrating an approach that may have potential for treating proteopathies.

  • Zhaoyang Li
  • , Cen Wang
  •  & Boxun Lu

• Letter | 04 September 2019

  Straightforward access to N-trifluoromethyl amides, carbamates, thiocarbamates and ureas

  N-trifluoromethyl analogues of amides and related carbonyl compounds are prepared via bench-stable carbamoyl fluoride building blocks.

  • Thomas Scattolin
  • , Samir Bouayad-Gervais
  •  & Franziska Schoenebeck

• Letter | 28 August 2019

  Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation

  The palmitoylation of STAT3 is mediated by fatty acids and/or the palmitoyl acyltransferase ZDHHC19, and deregulation of this palmitoylation has a role in inflammation and tumorigenesis.

  • Jixiao Niu
  • , Yang Sun
  •  & Xu Wu

• Article | 31 July 2019

  Structure and mechanism of the cation–chloride cotransporter NKCC1

  The cryo-EM structure of the zebrafish cation–chloride cotransporter NKCC1 reveals the domain organization, ion translocation pathway, ion-binding sites and key residues for binding activity, providing insights into the activity of this family of transporter proteins with key roles in physiology.

  • Thomas A. Chew
  • , Benjamin J. Orlando
  •  & Liang Feng

• Technology Feature | 23 July 2019

  The computational protein designers

  A new breed of protein engineers is finding that the best way to create a molecule is to build it from scratch.

  • Jeffrey M. Perkel

• News & Views | 19 June 2019

  A universal control system for synthetic gene networks

  A module for implementing robust feedback control in synthetic cellular networks has been reported. Its design is first proved mathematically to be universal for all networks, and then implemented in living cells.

  • Noah Olsman
  •  & Johan Paulsson

• Article | 19 June 2019

  Large-scale chemical–genetics yields new M. tuberculosis inhibitor classes

  A high-throughput chemical–genetic screening approach for the discovery of targets and chemicals to treat Mycobacterium tuberculosis yields tenfold more hit compounds than conventional whole-cell screening methods.

  • Eachan O. Johnson
  • , Emily LaVerriere
  •  & Deborah T. Hung

• News & Views | 10 June 2019

  Enzymes that detoxify marine toxins

  Potent microbial toxins found in shellfish are possible starting points for drug discovery, but analogues are needed for biological testing. Toxin-modification enzymes now suggest a new approach for producing these analogues.

  • Monica E. McCallum
  •  & Emily P. Balskus

• News & Views | 05 June 2019

  Predators affect competitors’ coexistence through fear effects

  Predators are often thought to structure ecological communities by consuming competitively dominant species, which promotes the coexistence of species. But an alternative mechanism might involve the effects of fear.

  • Oswald J. Schmitz

• Article | 03 June 2019

  Mapping human microbiome drug metabolism by gut bacteria and their genes

  High-throughput genetic analyses combined with mass spectrometry reveal that the gene products of diverse human gut bacteria affect a wide range of oral drugs, as well as drug metabolism in mice.

  • Michael Zimmermann
  • , Maria Zimmermann-Kogadeeva
  •  & Andrew L. Goodman

• News & Views | 27 May 2019

  Catalytic machinery of enzymes expanded

  Only a few types of natural amino-acid residue are used directly by enzymes to catalyse reactions. The incorporation of an unnatural residue into an enzyme shows how the catalytic repertoire of enzymes can be enlarged.

  • Adam Nelson

• Letter | 27 May 2019

  Design and evolution of an enzyme with a non-canonical organocatalytic mechanism

  A hydrolytic enzyme with a non-canonical organocatalytic mechanism was generated by introducing N_δ-methylhistidine into a designed active site using engineered translation components, allowing optimization of enzyme performance using laboratory evolution.

  • Ashleigh J. Burke
  • , Sarah L. Lovelock
  •  & Anthony P. Green

• News & Views | 16 May 2019

  Construction of an Escherichia coli genome with fewer codons sets records

  The biggest synthetic genome so far has been made, with a smaller set of amino-acid-encoding codons than usual — raising the prospect of encoding proteins that contain unnatural amino-acid residues.

  • Benjamin A. Blount
  •  & Tom Ellis

• Nature Podcast | 15 May 2019

  Podcast: Recoding genomes, and material from the Moon's far side

  Listen to the lastest science news, brought to you by Shamini Bundell and Nick Howe.

• News & Views | 08 May 2019

  Protein assembles into Archimedean geometry

  A natural protein has been engineered to self-associate into an architecture previously unknown among biological molecules: a cage structure based on one of the classic polyhedra identified by Archimedes.

  • Todd O. Yeates

• News & Views | 08 May 2019

  An ‘on’ switch for proteins

  Current methods for producing proteins that can be activated by light require knowledge of the protein’s active site, or can reduce the protein’s functionality. A technique that overcomes these issues has been devised.

  • Klaus Michael Hahn

• Article | 08 May 2019

  Time-resolved protein activation by proximal decaging in living systems

  The authors report a general strategy for in vivo protein activation using light-controlled proximal decaging directed by in silico screening.

  • Jie Wang
  • , Yuan Liu
  •  & Peng R. Chen

• Research Highlight | 21 March 2019

  This plant is hiding secret stores of an anti-malaria drug

  Discovery could lead to a more stable supply of the compound artemisinin, which is used when other therapies fail.

• Letter | 13 March 2019

  Discovery of a pathway for terminal-alkyne amino acid biosynthesis

  Microbial generation of a terminal-alkyne-containing amino acid can be encoded into E. coli and provides the potential for in vivo generation of proteins and natural products for click chemistry.

  • J. A. Marchand
  • , M. E. Neugebauer
  •  & M. C. Y. Chang

• News & Views | 08 March 2019

  Enzymes trapped and zapped for use outside cells

  Many enzymes cooperate with other proteins and small molecules to function. A strategy that mimics the confinement of such cooperative partners in cells might allow these enzymes to be used in applications outside biological systems.

  • Alison Narayan

• News | 27 February 2019

  Scientists brew cannabis using hacked beer yeast

  Researchers modify microbe to manufacture cannabis compounds including the psychoactive chemical THC.

  • Elie Dolgin

• Toolbox | 25 February 2019

  The race for enzymatic DNA synthesis heats up

  An alternative to chemical oligonucleotide synthesis inches closer to reality.

  • Jeffrey M. Perkel

• News | 21 February 2019

  Four new DNA letters double life’s alphabet

  Synthetic DNA seems to behave like the natural variety, suggesting that chemicals beyond nature’s four familiar bases could support life on Earth.

  • Matthew Warren

• News & Views | 13 February 2019

  Fresh evidence overturns the identification of a factor involved in blood-vessel dilation

  Nine years ago, the compound kynurenine was reported to be responsible for the dilation of blood vessels during a potentially fatal inflammatory condition. New evidence has now identified the true culprit.

  • David A. Kass

• Letter | 13 February 2019

  Singlet molecular oxygen regulates vascular tone and blood pressure in inflammation

  Singlet molecular oxygen, produced by indoleamine 2,3-dioxygenase 1 activity, gives rise to a signalling molecule that regulates arterial relaxation under inflammatory conditions.

  • Christopher P. Stanley
  • , Ghassan J. Maghzal
  •  & Roland Stocker

• Editorial | 06 February 2019

  Ultra-large virtual molecular libraries throw open chemical space

  A library of 350 million drug-like molecules points to potential drugs.

• News & Views | 06 February 2019

  Bigger is better in virtual drug screens

  A system has been devised that computationally screens hundreds of millions of drug candidates — all of which can be made on demand — against biological targets. This could help to make drug discovery more efficient.

  • David E. Gloriam

• Article | 06 February 2019

  Ultra-large library docking for discovering new chemotypes

  Using a make-on-demand library that contains hundreds-of-millions of molecules, structure-based docking was used to identify compounds that, after synthesis and testing, are shown to interact with AmpC β-lactamase and the D₄ dopamine receptor with high affinity.

  • Jiankun Lyu
  • , Sheng Wang
  •  & John J. Irwin

• Letter | 06 February 2019

  An N-nitrosating metalloenzyme constructs the pharmacophore of streptozotocin

  The metalloenzyme SznF catalyses the formation of an N–N bond in the biosynthesis of streptozotocin, providing insights into the enzymatic assembly of an N-nitroso group.

  • Tai L. Ng
  • , Roman Rohac
  •  & Emily P. Balskus

• News | 31 January 2019

  How machine learning could keep dangerous DNA out of terrorists’ hands

  Sophisticated algorithms could help DNA-synthesis companies avoid making dangerous organisms on demand.

  • Sara Reardon

• Article | 02 January 2019

  GABA_A receptor signalling mechanisms revealed by structural pharmacology

  Cryo-electron microscopy structures are reported in which the full-length human α1β3γ2L GABA_A receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA, and the benzodiazepines alprazolam and diazepam.

  • Simonas Masiulis
  • , Rooma Desai
  •  & A. Radu Aricescu

• Letter | 19 December 2018

  Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp³ C–H functionalization

  Evolved iron-containing enzymes based on cytochrome P450 achieve selective intermolecular alkylation of sp³ C–H bonds through a carbene C–H insertion strategy.

  • Ruijie K. Zhang
  • , Kai Chen
  •  & Frances H. Arnold

• News & Views | 12 December 2018

  Enzymes engineered to trap reaction intermediates

  Many enzymatic processes involve a mechanism in which reaction intermediates are covalently attached to the enzyme’s active site. A strategy has been devised that enables mimics of these intermediates to be visualized.

  • Andrew M. Gulick

• Letter | 12 December 2018

  Trapping biosynthetic acyl-enzyme intermediates with encoded 2,3-diaminopropionic acid

  A method for encoding the non-canonical amino acid 2,3-diaminopropionate into proteins allows key acyl intermediates in the biosynthesis of valinomycin to be trapped, providing insight into the oligomerization and cyclization reactions involved.

  • Nicolas Huguenin-Dezot
  • , Diego A. Alonzo
  •  & Jason W. Chin

• Letter | 05 December 2018

  A chemical defence against phage infection

  Streptomyces secondary metabolites provide a chemical defence against phage predation.

  • Sarah Kronheim
  • , Martin Daniel-Ivad
  •  & Karen L. Maxwell

• Research Highlight | 30 November 2018

  Light pulses prod artificial muscle into action

  An optical signal triggers mechanical motion thanks to a nerve junction constructed in the laboratory.

• Letter | 21 November 2018

  Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity

  Strains of methicillin-resistant Staphylococcus aureus use a prophage-encoded glycosyltransferase to alter the glycosylation of their wall teichoic acid and thereby evade antibody-mediated immune responses.

  • David Gerlach
  • , Yinglan Guo
  •  & Andreas Peschel

• News | 15 November 2018

  Ban on ‘gene drives’ is back on the UN’s agenda — worrying scientists

  Research is moving fast on the divisive genetic technology, which could help to eradicate diseases but also risks altering ecosystems in unpredictable ways.

  • Ewen Callaway

• News Feature | 07 November 2018

  Bottom-up biology

  Researchers are tearing up the biology rule books by trying to construct cells from scratch. A special issue explores the lessons being learnt about life.

• Editorial | 07 November 2018

  Focus on the benefits of building life’s systems from scratch

  Scientists have overturned the conventional top-down approach to studying cells to instead construct new cellular systems from the bottom up.

• News Feature | 07 November 2018

  How biologists are creating life-like cells from scratch

  Built from the bottom up, synthetic cells and other creations are starting to come together and could soon test the boundaries of life.

  • Kendall Powell

• Nature Podcast | 07 November 2018

  Podcast: Designer cells, and a Breakthrough researcher

  Benjamin Thompson and Shamini Bundell bring you this week's science news.

• Letter | 07 November 2018

  Design of amidobenzimidazole STING receptor agonists with systemic activity

  A small-molecule agonist for the cGAS–STING pathway has systemic activity in a mouse model of colon cancer.

  • Joshi M. Ramanjulu
  • , G. Scott Pesiridis
  •  & John Bertin

• Comment | 06 November 2018

  Which biological systems should be engineered?

  To solve real-world problems using emerging abilities in synthetic biology, research must focus on a few ambitious goals, argues Dan Fletcher.

  • Dan Fletcher

• Letter | 24 October 2018

  Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis

  The mechanism of glycogenesis, initiated by glycogenin, involves three distinct kinetic phases, with the final phase involving a refining process where only glucose is tolerated as a substrate.

  • Matthew K. Bilyard
  • , Henry J. Bailey
  •  & Benjamin G. Davis

• Letter | 15 October 2018

  A protein functionalization platform based on selective reactions at methionine residues

  This methionine-selective functionalization strategy uses hypervalent iodine reagents to introduce new groups via the formation of a sulfonium intermediate, which can then undergo further visible-light-mediated reactions to form a diverse range of protein conjugates.

  • Michael T. Taylor
  • , Jennifer E. Nelson
  •  & Matthew J. Gaunt

• Letter | 15 October 2018

  A metabolite-derived protein modification integrates glycolysis with KEAP1–NRF2 signalling

  Inhibition of the glycolytic enzyme PGK1 using a small molecular probe reveals a molecular link between glycolysis and the KEAP1–NRF2 signalling cascade.

  • Michael J. Bollong
  • , Gihoon Lee
  •  & Raymond E. Moellering

• Letter | 03 October 2018

  Asymmetric α-arylation of amino acids

  This approach introduces an aryl substituent to the α-carbon of amino acids without a transition-metal catalyst, and uses the inherent chirality of the amino acid itself as the source of asymmetry.

  • Daniel J. Leonard
  • , John W. Ward
  •  & Jonathan Clayden

• News & Views | 12 September 2018

  Designer proteins activate fluorescent molecules

  A computational method has been devised that allows a structural motif found in proteins, known as a β-barrel, to be designed to bind specifically to any small molecule, opening the door to biotechnological applications.

  • Roberto A. Chica

• News & Views | 04 September 2018

  DNA tags used to image sugar-bearing proteins on cells

  Methods for imaging sugars attached to proteins — the protein glycoforms — are of interest because glycoforms affect protein movement and localization in cells. A versatile approach is now reported that uses DNA as molecular identity tags.

  • Tadashi Suzuki