Synthetic biology articles within Nature Communications

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  • Article
    | Open Access

    Artificial genetic polymers (XNAs) have been explored for their nuclease activity, but XNAzymes have proven challenging to discover by in vitro selection. Here, the authors generate an efficient RNA-cleaving 2’-fluoroarabino nucleic acid enzyme (FANAzyme) by in vitro evolution using natural DNA polymerases.

    • Yajun Wang
    • , Arlene K. Ngor
    •  & John C. Chaput

  • Article
    | Open Access

    Cells communicate through chemical and mechanical signals but emulating these in non-living mimics has been challenging. Here the authors present a porous mimic with a DNA-hydrogel ‘nucleus’ that can communicate through diffusive protein signals.

    • Henrike Niederholtmeyer
    • , Cynthia Chaggan
    •  & Neal K. Devaraj

  • Article
    | Open Access

    Artificial gene circuits represent intellectual property that under some circumstances may need to be obfuscated to prevent discovery by third parties. Here the authors use encryption by overlapping recombinase sites and steganography by the introduction of superfluous components, to obscure circuit topology.

    • Oliver Purcell
    • , Jerry Wang
    •  & Timothy K. Lu

  • Article
    | Open Access

    The construction of complex RNA-delivered genetic circuits in mammalian cells is challenging, though offers advantages over DNA circuits in clinical use. Here the authors construct a set of logic gates that respond to multiple miRNAs and demonstrate an apoptosis-regulatory AND gate.

    • Satoshi Matsuura
    • , Hiroki Ono
    •  & Hirohide Saito

  • Article
    | Open Access

    Gene synthesis has expanded the ability to modify and create DNA sequences, with implications for biosurveillance. The authors use machine learning and codon theory to identify synthetic genes in Addgene data, and show that synthesis accelerates human-directed gene transfer across the tree of life.

    • Aditya M. Kunjapur
    • , Philipp Pfingstag
    •  & Neil C. Thompson

  • Article
    | Open Access

    RNA-encoded regulatory circuits are desirable because they do not integrate in the host and are less immunogenic, but the availability of regulatory devices is limited. Here the authors develop viral protease RNA-binding proteins and protease–protease genetic circuits that ultimately regulate mRNA translation.

    • Federica Cella
    • , Liliana Wroblewska
    •  & Velia Siciliano

  • Article
    | Open Access

    Designing split protein approaches is time consuming and often results in high background activity due to spontaneous assembly. Here the authors present an automated approach which uses a split energy scoring function to identify optimal protein split sites and reduces spontaneous assembly.

    • Onur Dagliyan
    • , Andrey Krokhotin
    •  & Nikolay V. Dokholyan

  • Article
    | Open Access

    The E. coli MinCDE system oscillates between cell poles to position the main division protein FtsZ. Here authors use in vitro reconstitution to show that MinDE oscillations also regulate unrelated membrane proteins spatiotemporally into patterns and gradients by forming a moving physical barrier.

    • Beatrice Ramm
    • , Philipp Glock
    •  & Petra Schwille

  • Article
    | Open Access

    Lipid-based membranes coupled to biochemical reaction networks can be difficult to implement in vitro. Here the authors use elastin-like peptides to create self-assembled vesicle structures containing transcription-translation systems for autonomous growth.

    • Kilian Vogele
    • , Thomas Frank
    •  & Tobias Pirzer

  • Article
    | Open Access

    Genome structural variation can play an important functional role in phenotypic diversity. Here the authors use the SCRaMbLE system on a ring synthetic chromosome V to generate complex rearrangements distinct from a rearranged linear chromosome.

    • Juan Wang
    • , Ze-Xiong Xie
    •  & Ying-Jin Yuan

  • Article
    | Open Access

    Tightly regulated promoters with strong inducibility and scalability are highly desirable for biological applications. Here the authors describe ‘Jungle Express’, a EilR repressor-based broad host system activated by cationic dyes.

    • Thomas L. Ruegg
    • , Jose H. Pereira
    •  & Michael P. Thelen

  • Article
    | Open Access

    Classic monodirectional promoters are of limited use for multiple gene co-expression. Here the authors generate a library of 168 bidirectional promoters for the yeast K. phaffii (syn. P. pastoris) with diverse expression profiles to optimize metabolic pathway design.

    • Thomas Vogl
    • , Thomas Kickenweiz
    •  & Anton Glieder

  • Article
    | Open Access

    Bacterially encoded environmental sensor proteins are potentially a rich source of transcriptional control but only a few have been harnessed for biotechnological applications. Here the authors develop a general strategy for designing custom-made monogenic synthetic sensors and validate the approach by designing two sense-and-respond regulators for benzoate.

    • Javier F. Juárez
    • , Begoña Lecube-Azpeitia
    •  & George M. Church

  • Article
    | Open Access

    Reducing aerobic ethanol production, a phenomenon referred to as the Crabtree effect, may open up new perspectives for using yeast as a cell factory. Here, the authors turn the Crabtree-positive yeast into Crabtree negative by combined engineering of cytosolic acetyl-CoA metabolism and mutating the RNA polymerase II mediator complex.

    • Zongjie Dai
    • , Mingtao Huang
    •  & Jens Nielsen

  • Article
    | Open Access

    Designer organelles with new biochemical functionalities are of great interest in synthetic biology and cellular engineering. Here the authors present a single-protein-based platform for generating synthetic membraneless compartments that is capable of enzymatically-triggered alterations to phase behavior and of recruiting and concentrating cargo proteins.

    • Benjamin S. Schuster
    • , Ellen H. Reed
    •  & Daniel A. Hammer

  • Perspective
    | Open Access

    Synthetic biology often views the organism as a chassis into which a circuit can be inserted. Here the authors explore the idea of the organism as a core aspect of design, aiding researchers in navigating the genetic space opened up by SCRaMbLE.

    • Erika Szymanski
    •  & Jane Calvert

  • Article
    | Open Access

    The ability to produce homogeneous glycoproteins is expected to advance fundamental understanding in glycoscience, but current in vivo-based production systems have several limitations. Here, the authors develop an E. coli extract-based one-pot system for customized production of N-linked glycoproteins.

    • Thapakorn Jaroentomeechai
    • , Jessica C. Stark
    •  & Matthew P. DeLisa

  • Article
    | Open Access

    The engineering of synthetic microbial communities necessitates the use of synthetic, orthogonal cell-to-cell communication channels. Here the authors present a library of characterised AHL-receiver devices and a software tool for the automatic identification of non-interfering chemical communication channels.

    • Nicolas Kylilis
    • , Zoltan A. Tuza
    •  & Karen M. Polizzi

  • Article
    | Open Access

    The absence of effective gene activators in bacteria limits regulated expression programs. Here the authors design synthetic bacterial CRISPR-Cas transcriptional activators that can be used to construct multi-gene programs of activation and repression.

    • Chen Dong
    • , Jason Fontana
    •  & Jesse G. Zalatan

  • Article
    | Open Access

    MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression but many quantitative aspects of miRNA biology remain to be elucidated. Based on a library of miRNA sensors, the authors quantify miRNA regulation at single cell level and develop a model to predict miRNA target interactions.

    • Jeremy J. Gam
    • , Jonathan Babb
    •  & Ron Weiss

  • Article
    | Open Access

    Control of transgene expression should ideally be easy and with minimal side effects. Here the authors present a synthetic biology-based approach in which the caffeine in coffee regulates a genetic circuit controlling glucagon-like peptide 1 expression in diabetic mice.

    • Daniel Bojar
    • , Leo Scheller
    •  & Martin Fussenegger

  • Article
    | Open Access

    Generating artificial cells able to carry out metabolic activities out-of-equilibrium is a current challenge in synthetic biology. Here the authors use a microfluidic platform for integration and analysis of minimal metabolic reactions in artificial microcompartments formed of water-in-oil droplets.

    • Thomas Beneyton
    • , Dorothee Krafft
    •  & Jean-Christophe Baret

  • Article
    | Open Access

    Pentatricopeptide repeat proteins bind single-stranded RNA and have been used to study ssRNA biology. Here the authors co-opt these proteins to target ssDNA and demonstrate specific binding of telomere sequences, the structural basis for ssDNA wrapping, and use them as potent telomerase inhibitors.

    • Henrik Spåhr
    • , Tiongsun Chia
    •  & Oliver Rackham

  • Article
    | Open Access

    The use of synthetic chromosomes and the recombinase-based SCRaMbLE system could enable rapid strain evolution through massive chromosome rearrangements. Here the authors present ReSCuES, which uses auxotrophic markers to rapidly identify yeast with rearrangements for strain engineering.

    • Zhouqing Luo
    • , Lihui Wang
    •  & Junbiao Dai

  • Article
    | Open Access

    The Sc2.0 project has built the Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system into their synthetic chromosomes. Here the authors use SCRaMbLE to rapidly develop, diversify and screen strains for diverse production and growth characteristics.

    • B. A. Blount
    • , G-O. F. Gowers
    •  & T. Ellis

  • Article
    | Open Access

    SCRaMbLE allows for the rapid and large scale rearrangement of genetic data in yeast carrying synthetic chromosomes. Here the authors demonstrate an in vitro use of the method to generate DNA libraries for optimization of biochemical reactions.

    • Yi Wu
    • , Rui-Ying Zhu
    •  & Jef D. Boeke

  • Article
    | Open Access

    SCRaMbLE has been used to rearrange synthetic chromosomes that have been introduced into host yeast. Here the authors produce semi-synthetic heterozygous diploid strains for rapid selection of phenotypes and map the rearrangements underlying selected phenotypes such as thermoresistance and caffeine resistance.

    • Michael J. Shen
    • , Yi Wu
    •  & Jef D. Boeke

  • Article
    | Open Access

    The SCRaMbLE system integrated into Sc2.0’s synthetic yeast chromosome project allows rapid strain evolution. Here the authors use a genetic logic gate to control induction of recombination in a haploid and diploid yeast carrying synthetic chromosomes.

    • Bin Jia
    • , Yi Wu
    •  & Ying-Jin Yuan

  • Article
    | Open Access

    Assembly of higher-order artificial vesicles can unlock new applications. Here, the authors use optical tweezers to construct user-defined 2D and 3D architectures of chemically distinct vesicles and demonstrate inter-vesicle communication and light-enabled compartment merging.

    • Guido Bolognesi
    • , Mark S. Friddin
    •  & Yuval Elani

  • Article
    | Open Access

    Synthetic biology principles are often used to design circuits that tune gene expression in response to changes in intracellular environments. Here the authors design a modular platform for intracellular protein sensing devices with transcriptional output.

    • Velia Siciliano
    • , Breanna DiAndreth
    •  & Ron Weiss

  • Article
    | Open Access

    Bacterial populations communicate with AI-2 signaling molecules, helping to coordinate biofilm development and other group behaviors. Here the authors design a genetic circuit for mammalian cells that allows them to sense bacterial populations and interfere with quorum communication.

    • Ferdinand Sedlmayer
    • , Dennis Hell
    •  & Martin Fussenegger

  • Article
    | Open Access

    The translation of heterologous proteins places a burden on host cell resources, affecting growth and productivity. Here the authors develop a cell-free assay to measure resource consumption and predict in vivo burden.

    • Olivier Borkowski
    • , Carlos Bricio
    •  & Tom Ellis

  • Article
    | Open Access

    Two-component systems are a major family of signal transduction pathways and a rich source of sensors for biotechnology. Here, the authors develop a general method for rationally tuning two-component system input detection thresholds via specific point mutations in sensor histidine kinase proteins.

    • Brian P. Landry
    • , Rohan Palanki
    •  & Jeffrey J. Tabor

  • Article
    | Open Access

    Self-assembling proteins have important applications in industrial technologies, but it is difficult to predict how mutations affect assembly. Here the authors present SyMAPS, coupling comprehensive codon mutagenesis with high-throughput sequencing, and apply it to bacteriophage capsid protein.

    • Emily C. Hartman
    • , Christopher M. Jakobson
    •  & Danielle Tullman-Ercek

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