Molecular engineering articles within Nature Communications

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  • 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

  • Article
    | Open Access

    Tweaking immune characteristics of donors and recipients could allow for successful cross-species organ transplantation. Here, the authors show that an anti-CD40 antibody therapy of baboons that received heart transplants from genetically modified pigs is key to their long-term survival.

    • Muhammad M. Mohiuddin
    • , Avneesh K. Singh
    •  & Keith A. Horvath

  • Article
    | Open Access

    Droplet-based optical polymerase sorting employs a fluorescent sensor to monitor polymerase activity inside the microenvironment of uniform water-in-oil emulsions. Here, the authors use this technique to select and isolate single cells for evolution of an unnatural nucleic acid polymerase.

    • Andrew C. Larsen
    • , Matthew R. Dunn
    •  & John C. Chaput

  • Article
    | Open Access

    Modification of the spliceosome is being tested as a potential therapy for exon-skipping diseases, such as spinal muscular atrophy (SMA). Here the authors show that 70K and stem loop IV structural elements of a modified U1 particle are essential for splicing enhancement and effective treatment of SMA mice.

    • Malgorzata Ewa Rogalska
    • , Mojca Tajnik
    •  & Franco Pagani

  • Article
    | Open Access

    Early cells likely consisted of fatty acid vesicles enclosing magnesium-dependent ribozymes. Here, the authors show that fatty acid derivatives can form vesicles that, unlike those formed from only unmodified fatty acids, are stable in the presence of magnesium and could support ribozyme catalysis.

    • Katarzyna P. Adamala
    • , Aaron E. Engelhart
    •  & Jack W. Szostak

  • Article
    | Open Access

    Flexible or disordered domains often hinder the purification of proteins involved in functional interactions. Here the authors describe an approach that enables the production of stable and functional complexes of otherwise unstable proteins in quantities sufficient for structural and functional studies.

    • Nicolas Levy
    • , Sylvia Eiler
    •  & Marc Ruff

  • Article
    | Open Access

    Opiates—the gold standard for pain relief—are currently produced by extraction from opium poppies. Here the authors show that bacteria can serve as an efficient and flexible platform for the production of opiates by demonstrating the total synthesis of Thebaine and hydrocodone from stepwise fermentation in E. coli.

    • Akira Nakagawa
    • , Eitaro Matsumura
    •  & Hiromichi Minami

  • Article
    | Open Access

    There is enormous potential in combining the capabilities of the biological and the solid-state to create hybrid engineered systems. Here, the authors develop a technique to incorporate and activate ATPases in in vitromembranes to produce energy-harvestable currents to power an integrated circuit.

    • Jared M. Roseman
    • , Jianxun Lin
    •  & Kenneth L. Shepard

  • Article
    | Open Access

    Living cells have to interpret and react to changes in local environmental conditions. Here the authors exploit that by combining magnetic nanoparticles and bacterial quorum sensing to investigate and convey alterations in the molecular landscape.

    • Jessica L. Terrell
    • , Hsuan-Chen Wu
    •  & William E. Bentley

  • Article
    | Open Access

    The inability to produce recombinant phosphoproteins has hindered research into their structure and function. Here the authors develop a cell-free protein synthesis platform to site-specifically incorporate phosphoserine into proteins at high yields, and recapitulate a MEK1 kinase signalling cascade.

    • Javin P. Oza
    • , Hans R. Aerni
    •  & Michael C. Jewett

  • Article
    | Open Access

    The effects of protein phosphorylation, a common post-translational modification, are difficult to study using recombinant proteins. Here the authors use genomically engineered E. colito enhance translation systems that express phosphor-serine containing proteins, and use these systems to produce phosphorylated MEK1 kinase.

    • Natasha L. Pirman
    • , Karl W. Barber
    •  & Jesse Rinehart

  • Article
    | Open Access

    Super-resolution imaging of microtubules requires labels that increase their apparent diameter, making it difficult to resolve individual microtubules within a bundle. Here, the authors develop single-chain antibody fragments against tubulin that enable closely spaced individual microtubules to be distinguished in cells.

    • Marina Mikhaylova
    • , Bas M. C. Cloin
    •  & Lukas C Kapitein

  • Article
    | Open Access

    Antisense oligonucleotides (ASOs) can repress the expression of specific genes. Here, the authors show that a DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from ASOs is more potent in suppressing target gene expression, and causes a less adverse effect in mouse liver.

    • Kazutaka Nishina
    • , Wenying Piao
    •  & Takanori Yokota

  • Article
    | Open Access

    Endogenous fungal gene promoters can be hundreds of base pairs long, limiting their use in synthetic biology and biotechnology. Here Redden and Alper screen a library of synthetic promoter elements to generate compact DNA sequences of ∼100 base pairs able to drive high levels of gene expression.

    • Heidi Redden
    •  & Hal S. Alper

  • Article
    | Open Access

    Synthetic engineering of complex pathways is often hindered by pathway branching and generation of non-target compounds. Here, the authors show that by judicious combination of moderately selective enzyme variants, a non-natural C50 carotenoid can be generated in bacteria with minimal production of unwanted compounds.

    • Maiko Furubayashi
    • , Mayu Ikezumi
    •  & Daisuke Umeno

  • Article
    | Open Access

    The ability to contain and destroy synthetically engineered microorganisms is an important consideration with environmental, industrial and intellectual property implications. Here Caliando et al. design and demonstrate a stably integrated CRISPR-based system for targeted DNA destruction.

    • Brian J. Caliando
    •  & Christopher A. Voigt

  • Article
    | Open Access

    Retinal-bound opsins are widely used tools for optical control of neuronal activity in vivo, so called optogenetics. Here, using molecular simulations, biochemistry, electrophysiology and X-ray crystallography, the authors present new molecular design principles for the generation of blue-shifted variants of microbial rhodopsins.

    • Hideaki E. Kato
    • , Motoshi Kamiya
    •  & Osamu Nureki

  • Article |

    Protein switches have a number of potential biotechnological applications. Here, the authors present fusions of maltose-binding protein with TEM1 β-lactamase as multi-input allosteric protein switches that can be controlled by temperature and pH in the presence of the effector.

    • Jay H. Choi
    • , Abigail H. Laurent
    •  & Marc Ostermeier

  • Article |

    Photoreceptor-based photoswitches have proved to be powerful tools for the specific control of protein activity in live cells. Here the authors describe Magnets, a new set of photoswitches based on the Vivid photoreceptor with enhanced hetero-dimerization specificity and variable activation kinetics.

    • Fuun Kawano
    • , Hideyuki Suzuki
    •  & Moritoshi Sato

  • Article |

    Pentatricopeptide repeat (PPR) proteins bind RNA and control diverse aspects of RNA metabolism in eukaryotic cells. Here, Coquille et al.present the crystal structures of several engineered PPR domains, elucidate their RNA binding mode and suggest paths to the design of modular, sequence-specific PPR domains.

    • Sandrine Coquille
    • , Aleksandra Filipovska
    •  & Oliver Rackham

  • Article
    | Open Access

    Activating mutations of the tyrosine kinase Kit are commonly found in mast cell neoplasms and gastrointestinal stromal tumours. Here the authors show that mutant Kit, through the activation of PI3K and STAT3 pathways, elicits proliferative and survival signals from endolysosomes and from the endoplasmic reticulum.

    • Yuuki Obata
    • , Shota Toyoshima
    •  & Ryo Abe

  • Article
    | Open Access

    Brain–machine interfaces offer the possibility of controlling prosthetic devices using changes in brain activity. Folcher et al.couple such a system wirelessly to an optogenetic implant in mice to control expression of a transgene, demonstrating its potential for mind-controlled drug delivery.

    • Marc Folcher
    • , Sabine Oesterle
    •  & Martin Fussenegger

  • Article |

    Engineering gene expression systems that can be programmed to respond to specific environmental conditions is challenging. Here, the authors develop a synthetic bow-tie circuit that is able to sense signals from microRNA molecules and affect a change in protein dynamics in mammalian cells.

    • Laura Prochazka
    • , Bartolomeo Angelici
    •  & Yaakov Benenson

  • Article |

    Toggle switches can be engineered using pairs of transcriptional repressors; however, their bistability depends on nonlinear DNA-binding properties. Lebar et al. design a circuit that ensures bistability by artificially generating nonlinearity and use it to construct a toggle from programmable DNA-binding domains.

    • Tina Lebar
    • , Urban Bezeljak
    •  & Roman Jerala

  • Article
    | Open Access

    Constructing gene circuits with predefined behaviours is typically done on a case-by-case basis. Schaerli et al.instead computationally explore the design space for 3-node networks that generate a stripe in response to a morphogen gradient, and build networks based on their simplest possible forms.

    • Yolanda Schaerli
    • , Andreea Munteanu
    •  & Mark Isalan

  • Article
    | Open Access

    Propane is the main component of liquid petroleum gas and has a wide variety of commercial applications. Here, the authors engineer a synthetic metabolic pathway in E. coli, and demonstrate for the first time the renewable production of propane.

    • Pauli Kallio
    • , András Pásztor
    •  & Patrik R. Jones

  • Article |

    Optimizing cell-surface biological reactions is an important goal of biotechnology and industrial processes. Here the authors use macromolecular crowding to enhance the enzymatic conversion of red blood cells to the universal type O blood type, using orders of magnitude less enzyme than was previously required.

    • Rafi Chapanian
    • , David H. Kwan
    •  & Jayachandran N Kizhakkedathu

  • Article
    | Open Access

    The ability to control antibody binding could have important medical implications. Here, the authors present a method to engineer phosphatase-controllable antibodies that bind to a specific recognition site in the presence of two biomarker inputs.

    • Smita B. Gunnoo
    • , Helene M. Finney
    •  & Benjamin G. Davis

  • Article
    | Open Access

    Neural circuits are functional ensembles of neurons that are selectively interconnected by chemical or electrical synapses. Here the authors describe an approach to the study of neural circuits in C. eleganswhereby electrical synapses are introduced between previously unconnected neurons to reprogram behaviour.

    • Ithai Rabinowitch
    • , Marios Chatzigeorgiou
    •  & William R. Schafer

  • Article |

    Antibody–antigen recognition is one of the important aspects of immunity, but the nanomechanical process of this recognition is not fully understood. Here, using high-speed atomic force microscopy, the authors observe that on membranes containing a high density of immobile antigens antibodies move in a ‘random walking’ motion.

    • Johannes Preiner
    • , Noriyuki Kodera
    •  & Peter Hinterdorfer

  • Article |

    In vitro biochemical pathways could provide the high yields required for economical commodity chemical production, but require circuitry development to regulate high-energy cofactors. Here, the authors design and test a simple purge valve system to maintain NADP+/NADPH balance in E. coli.

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

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