Molecular engineering articles within Nature Communications

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  • Article
    | Open Access

    With the growing threat of antibiotic resistance, unconventional approaches to antimicrobial discovery are needed. Here, the authors present a peptide topology that mimics virus architecture and assembles into antimicrobial capsids that disrupt bacterial membranes upon contact.

    • Emiliana De Santis
    • , Hasan Alkassem
    •  & Maxim G. Ryadnov

  • Article
    | Open Access

    Pathologies related to protein:protein interaction are hard to treat but cystine-dense peptides have the potential to disrupt such interactions. Here the authors develop a high-diversity mammalian cell screen for cystine-dense peptides with drug potential and use it to identify a YAP:TEAD inhibitor.

    • Zachary R. Crook
    • , Gregory P. Sevilla
    •  & James M. Olson

  • Article
    | Open Access

    E3 ubiquitin ligases regulate biological functions by ubiquitinating defined substrate proteins but overlapping specificities complicate the identification of E3-substrate relationships. Here, the authors construct an orthogonal UB transfer cascade and identify specific substrates of the E3 enzyme E6AP.

    • Yiyang Wang
    • , Xianpeng Liu
    •  & Jun Yin

  • Article
    | Open Access

    Ligand-induced biased signaling is thought to result in part from ligand-specific receptor conformations that cause the engagement of distinct effectors. Here the authors trace and evaluate the impact of mutations of the β2–adrenergic receptor on multiple signaling outputs to provide structural-level insight into the determinants of GPCR functional selectivity.

    • Anne-Marie Schönegge
    • , Jonathan Gallion
    •  & Michel Bouvier

  • Article
    | Open Access

    To restore sight after retinal degeneration, one approach is to express light-sensitive proteins in remaining cells. Here the authors combine a light-sensitive engineered G protein-coupled receptor and ion channels to restore ON and OFF responses as well as superior visual pattern discrimination.

    • Michael H. Berry
    • , Amy Holt
    •  & Ehud Y. Isacoff

  • Article
    | Open Access

    Lanthipeptides are a class of cyclic post-translationally modified peptides with potential drug-like properties. Here the authors develop a phage display system by expressing lanthipeptide precursors as C-terminal fusions to the phage M13 coat protein pIII in E. coli along with the heterologous modifying enzymes.

    • Johannes H. Urban
    • , Markus A. Moosmeier
    •  & Josef Prassler

  • Article
    | Open Access

    Proteases are promising therapeutics to treat diseases such as hemophilia which are due to endogenous protease deficiency. Here the authors use phage-assisted continuous evolution to evolve a variant TEV protease with altered target peptide sequence specificities.

    • Michael S. Packer
    • , Holly A. Rees
    •  & David R. Liu

  • Article
    | Open Access

    Genetic isolation of a genetically modified organism represents a useful strategy for biocontainment. Here the authors use dCas9-VP64-driven gene expression to construct a ‘species-like’ barrier to reproduction between two otherwise compatible populations.

    • Maciej Maselko
    • , Stephen C. Heinsch
    •  & Michael J. Smanski

  • Article
    | Open Access

    CRISPR-Cas9-based gene editing involves double-strand breaks at target sequences, which are often repaired by mutagenic non-homologous end-joining. Here the authors use Cas9 nickases to generate coordinated single-strand breaks in donor and target DNA for precise homology-directed gene editing.

    • Xiaoyu Chen
    • , Josephine M. Janssen
    •  & Manuel A. F. V. Gonçalves

  • Article
    | Open Access

    A major drawback in the clinical use of the oral anticoagulants that directly inhibit factor Xa in order to prevent blood clot formation is the potential for life threatening bleeding events. Here the authors describe factor Xa variants that are refractory to inhibition by these anticoagulants and could serve as rescue agents in treated patients.

    • Daniël Verhoef
    • , Koen M. Visscher
    •  & Mettine H. A. Bos

  • Article
    | Open Access

    Designer organelles could allow the isolation of synthetic biological pathways from endogenous components of the host cell. Here the authors engineer a peroxisomal protein import pathway orthogonal to the naturally occurring system.

    • Laura L. Cross
    • , Rupesh Paudyal
    •  & Stuart L. Warriner

  • Article
    | Open Access

    Split fluorescent proteins (FPs) have been widely used to visualise proteins in cells. Here the authors develop a screen for engineering new split FPs, and report a yellow-green split-mNeonGreen2 with reduced background, a red split-sfCherry2 for multicolour labeling, and its photoactivatable variant for super-resolution use.

    • Siyu Feng
    • , Sayaka Sekine
    •  & Bo Huang

  • Article
    | Open Access

    Humans are less sensitive to the therapeutic effects of botulinum neurotoxin B (BoNT/B) than the animal models it is tested on due to differences between the human and the mouse receptors. Here, the authors engineer BoNT/B to improve its affinity to human receptors and enhance its therapeutic efficacy.

    • Liang Tao
    • , Lisheng Peng
    •  & Min Dong

  • Article
    | Open Access

    Cryptochrome 2 (CRY2) from A. thaliana can be used to control light-dependent protein homo-oligomerization, but the molecular mechanism of CRY2 clustering is not known, limiting its application. Here the authors identify determinants of CRY2 clustering and engineer fusion partners to modulate clustering efficiency.

    • Hyerim Park
    • , Na Yeon Kim
    •  & Won Do Heo

  • Article
    | Open Access

    The depletion of antigen-specific, deleterious antibodies during therapy and diagnosis remains an unsolved challenge. Here the authors develop ‘Seldegs’, antigens linked to human Fc fragments with high affinity for the neonatal Fc receptor FcRn, to deplete MOG- and HER2-specific antibodies in mice.

    • Siva Charan Devanaboyina
    • , Priyanka Khare
    •  & E. Sally Ward

  • Article
    | Open Access

    The leakiness of commonly used genetic components can make the construction of complex synthetic circuits difficult. Here the authors construct NOR gate architecture, using dCas9 fused to the chromatin remodeller Mxi1, that can be wired together into complex circuits.

    • Miles W. Gander
    • , Justin D. Vrana
    •  & Eric Klavins

  • Article
    | Open Access

    Terpenes are bioactive natural products derived from plants with several commercial applications. Here, the authors engineer a cell-free system composed of 27 enzymes that convert glucose into terpenes, highlighting the potential of synthetic biochemistry approaches for biocompounds production.

    • Tyler P. Korman
    • , Paul H. Opgenorth
    •  & James U. Bowie

  • Article
    | Open Access

    The properties of many transmembrane or aggregation-prone proteins make them difficult to recombinantly express. Here the authors use a modified N-terminal domain of a spider silk protein to express and purify several difficult to express proteins at levels considerably higher than with conventional tags.

    • Nina Kronqvist
    • , Médoune Sarr
    •  & Jan Johansson

  • Article
    | Open Access

    Light-sensitive regulators of protein kinases could offer valuable insights into intracellular signalling. Here the authors design an optogenetic inhibitor of c-Jun N-terminal kinase (JNK) and show evidence for resonance in JNK signalling circuits in neurons, and use the same design principle to develop an inhibitor for p38MAPK.

    • Raquel M. Melero-Fernandez de Mera
    • , Li-Li Li
    •  & Michael J. Courtney

  • Article
    | Open Access

    Synthetic circuits in host cells compete with endogenous processes for limited resources. Here the authors use MazF to funnel cellular resources to a synthetic circuit to increase product production and demonstrate how resource allocation can be manipulated.

    • Ophelia S. Venturelli
    • , Mika Tei
    •  & Adam P Arkin

  • Article
    | Open Access

    Retinal vascular disease treatments involve frequent pharmacological intraocular administrations. Here the authors present a method to increase the half-life of injected drugs by fusing these to a hyaluronan-binding peptide, which might lead to less frequent retinal disease treatments.

    • Joy G. Ghosh
    • , Andrew A. Nguyen
    •  & Michael Roguska

  • Article
    | Open Access

    The production of short chain fatty acids by microorganisms has numerous industrial and biofuel applications. Here the authors reprogrammeS. cerevisiaefatty acid synthase with five mutations to produce C6- and C8-fatty acids and identify thioesterases responsible for hydrolysis of short chain acyl-CoA hydrolysis.

    • Jan Gajewski
    • , Renata Pavlovic
    •  & Martin Grininger

  • Article
    | Open Access

    Existing DNA based circuits, designed to perform logic operations and signal processing, are generally responsive to DNA or RNA inputs. Here, the authors show that antibodies can actuate DNA logic gates, opening the way to applications of DNA computing in diagnostics and biomedicine.

    • Wouter Engelen
    • , Lenny H. H. Meijer
    •  & Maarten Merkx

  • Article
    | Open Access

    Photosynthesis uses only a limited range of solar radiation. Here, Graysonet al. genetically incorporated the yellow fluorescent protein (YFP) chromophore into a bacterial photosystem, and show that energy harvested by reaction centre–YFP complexes can augment photosynthesis in vivo.

    • Katie J. Grayson
    • , Kaitlyn M. Faries
    •  & C. Neil Hunter

  • Article
    | Open Access

    Precision genome engineering using homology donors and the endogenous DNA break repair machinery and recently CRISPR-Cas9 targeted APOBECs have been demonstrated. Here the authors design zinc-finger and TALE chimeric deaminases and investigate editing efficiency and off-target effects.

    • Luhan Yang
    • , Adrian W. Briggs
    •  & George Church

  • Article
    | Open Access

    Plant synthetic biology offers the potential to re-engineer crops, but requires efficient methods to prepare constructs for transformation. Here Shih et al. develop jStack, a method that utilizes yeast homologous recombination and a library of DNA parts, to efficiently assemble plant transformation vectors.

    • Patrick M. Shih
    • , Khanh Vuu
    •  & Dominique Loqué

  • Article
    | Open Access

    Restoring lost excitability of injured tissue is a paramount of regenerative medicine. By using a combined expression of bacterial voltage-gated Na+ channel, Kir2.1, and connexin-43 in non-excitable human fibroblasts, here the authors generate excitable cells that rescue action potential conduction in an in vitromodel of cardiac fibrosis.

    • Hung X. Nguyen
    • , Robert D. Kirkton
    •  & Nenad Bursac

  • Article
    | Open Access

    Reversible manipulation of cell-cell interactions has potential applications in basic research and cell-based therapy. Here the authors control cell-cell adhesion in vitrowith light, by modifying the surface sugars of cells to display β-cyclodextrin, which recognises one isoform of light-isomerizable azobenzene linkers.

    • Peng Shi
    • , Enguo Ju
    •  & Xiaogang Qu

  • Article
    | Open Access

    In the construction of single fluorescent protein biosensors, selection of the insertion point of a fluorescent protein into a ligand-binding domain is a rate-limiting step. Here, the authors develop an unbiased, high-throughput approach, called domain insertion profiling with DNA sequencing (DIP-seq), to generate a novel trehalose biosensor.

    • Dana C. Nadler
    • , Stacy-Anne Morgan
    •  & David F. Savage

  • Article
    | Open Access

    S.Typhimurium can grow selectively on tumours and decreases the cellular levels of the multidrug resistance transporter Pgp. Here, the authors reveal the SipA-dependent mechanism of Pgp down-regulation and produce a SipA-based gold nanoparticle that increases sensitivity to the anticancer drug doxorubicin.

    • Regino Mercado-Lubo
    • , Yuanwei Zhang
    •  & Beth A. McCormick

  • Article
    | Open Access

    Exosomes have been identified as promising vehicles for the in vivodelivery of therapeutic molecules. Here the authors design a system to load protein cargos into exosomes during their biogenesis using optogenetic control of protein-protein interactions between the cargo and an exosome-localized partner.

    • Nambin Yim
    • , Seung-Wook Ryu
    •  & Chulhee Choi

  • Article
    | Open Access

    Noscapine is a potential anticancer drug that is traditionally isolated from the opium poppy Papaver somniferum. Here, Li and Smolke reconstitute the noscapine gene cluster in Saccharomyces cerevisiae, to achieve the microbial production of noscapine and related pathway intermediates, and provide new insights into the biosynthesis of noscapine.

    • Yanran Li
    •  & Christina D. Smolke

  • Article
    | Open Access

    Bacteria of the genus Streptomyces produce a great variety of natural products, the biosynthesis of which is subject to complex regulatory networks. Here the authors present a high-resolution, genome-wide analysis of the transcriptome and translatome of Streptomyces coelicolorunder various growth conditions.

    • Yujin Jeong
    • , Ji-Nu Kim
    •  & Byung-Kwan Cho

  • Article
    | Open Access

    Loss-of-function approaches are fundamental for dissecting the roles played by genes but methods to simultaneously perturb several proteins in the same mammalian cell are scarce. Here the authors harness the plant auxin and jasmonate hormone-degradation pathways and RNAi technology, to control the levels of two proteins and validate its application in stem cells.

    • Ran Brosh
    • , Iryna Hrynyk
    •  & Ihor R. Lemischka

  • Article
    | Open Access

    The excipients used to solubilise hydrophobic drugs sometimes interfere with drug behaviour or induce adverse side effects once injected. Here, the authors use a low-temperature process to obtain surfactant-stripped micelles with high drug concentration for delivery of a wide range of hydrophobic cargoes.

    • Yumiao Zhang
    • , Wentao Song
    •  & Jonathan F. Lovell

  • Article
    | Open Access

    DNA nanostructures have the potential to be powerful tools in many areas of biology however they are difficult to manufacture completely in vivo. Here the authors combine RNA hairpins and reverse transcription to generate and assemble a complex DNA structure inside the cellular environment.

    • Johann Elbaz
    • , Peng Yin
    •  & Christopher A. Voigt

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