Synthetic biology

  • Perspective
    | Open Access

    Synthetic biology engineering principles enable two-way communication between living and inanimate substrates. Here the authors consider the development of this bio-informational exchange and propose cyber-physical architectures and applications.

    • Thomas A. Dixon
    • , Thomas C. Williams
    •  & Isak S. Pretorius
  • Article
    | Open Access

    The PAM specificity of SpCas9 can be altered with positive selection during directed evolution. Here the authors use simultaneous positive and negative selection to improve activity on NAG PAMs while reducing activity on NGG PAMs.

    • Gregory W. Goldberg
    • , Jeffrey M. Spencer
    •  & Marcus B. Noyes
  • Article
    | Open Access

    Genetic circuits can be engineered to generate predefined outcomes, however host context is a crucial factor in performance. Here the authors characterise twenty NOT gates in seven different bacteria to understand and predict interoperability and portability across hosts.

    • Huseyin Tas
    • , Lewis Grozinger
    •  & Ángel Goñi-Moreno
  • Article
    | Open Access

    Stochastic fluctuations at the transcriptional level contribute to heterogeneity in isogenic cell populations. Here, the authors engineer TuNR which modulates the variability in gene expression of endogenous human genes independent of their mean expression.

    • Alain R. Bonny
    • , João Pedro Fonseca
    •  & Hana El-Samad
  • Article
    | Open Access

    Citrullination of arginine is crucial for several physiological processes. Here the authors report the site-specific incorporation of citrulline into proteins in mammalian cells using an engineered tRNA synthetase/tRNA pair and a photocaged-citrulline.

    • Santanu Mondal
    • , Shu Wang
    •  & Paul R. Thompson
  • Article
    | Open Access

    A fundamental function of living systems is regenerating essential components. Here the authors design an artificial cell using a minimal transcription-translation system in microfluidic reactors for sustained regeneration of multiple essential proteins.

    • Barbora Lavickova
    • , Nadanai Laohakunakorn
    •  & Sebastian J. Maerkl
  • Perspective
    | Open Access

    A key security challenge with biosecurity threats is determining the responsible actor. In this Perspective, the authors review recent developments in using genetic sequence to assign a lab-of-origin and the potential protection it provides against misuse of synthetic biology.

    • Gregory Lewis
    • , Jacob L. Jordan
    •  & Thomas V. Inglesby
  • Review Article
    | Open Access

    Large-scale meat production can have negative impacts on public health, the environment and animal welfare. In this Review, the authors consider plant-based and cell-based approaches to meat production and the challenges they face.

    • Natalie R. Rubio
    • , Ning Xiang
    •  & David L. Kaplan
  • Article
    | Open Access

    The potential for accidental or deliberate misuse of biotechnology is of concern for international biosecurity. Here the authors apply machine learning to DNA sequences and associated phenotypic data to facilitate genetic engineering attribution and identify country-of-origin and ancestral lab of engineered DNA sequences.

    • Ethan C. Alley
    • , Miles Turpin
    •  & Kevin M. Esvelt
  • Perspective
    | Open Access

    Advances in our ability to manipulate genetics leads to deeper understanding of biological systems. In this Perspective, the authors argue that synthetic genomics facilitates complex modifications that open up new areas of research.

    • Alessandro L. V. Coradini
    • , Cara B. Hull
    •  & Ian M. Ehrenreich
  • Article
    | Open Access

    The success of protein evolution is dependent on the sequence context mutations are introduced into. Here the authors present UMIC-seq that allows consensus generation for closely related genes by using unique molecular identifiers linked to gene variants.

    • Paul Jannis Zurek
    • , Philipp Knyphausen
    •  & Florian Hollfelder
  • Article
    | Open Access

    Large volumes of true random numbers are needed for increasing requirements of secure data encryption. Here the authors use the stochastic nature of DNA synthesis to obtain millions of gigabytes of unbiased randomness.

    • Linda C. Meiser
    • , Julian Koch
    •  & Robert N. Grass
  • Article
    | Open Access

    Automated design tools and tailored subunits are beneficial in fine-tuning all components of a complex genetic circuit. Here the authors create E. coli and B. subtilis promoter libraries using FACS and HTS, from which an online promoter design tool has been developed using CNN.

    • Maarten Van Brempt
    • , Jim Clauwaert
    •  & Marjan De Mey
  • Article
    | Open Access

    Current efforts to establish synthetic carbon fixation in model heterotrophs rely on expression of heterologous enzymes. Here, the authors explore the presence and activity of a latent CO2-assimilation pathway in E. coli based only on endogenous enzymes and a reversible decarboxylase.

    • Ari Satanowski
    • , Beau Dronsella
    •  & Arren Bar-Even
  • Article
    | Open Access

    The design and optimisation of 3D DNA-origami can be a barrier to rapid application. Here the authors design barrel structure of stacked 2D double helical rings with complex surface patterns.

    • Shelley F. J. Wickham
    • , Alexander Auer
    •  & William M. Shih
  • Article
    | Open Access

    Accurately predicting the behaviour of a genetic circuit remains difficult due to the lack of modularity. Here the authors quantify the effects of resource loading in mammalian systems and develop an endoribonuclease-based feedfoward controller to adapt gene expression to the effects of resource loading.

    • Ross D. Jones
    • , Yili Qian
    •  & Domitilla Del Vecchio
  • Article
    | Open Access

    Building regulatory networks often requires trade-offs between accuracy and speed. Here the authors show in a bistable network the transition from a slow decision making system to a rapid one dominated by small number fluctuations.

    • Ferdinand Greiss
    • , Shirley S. Daube
    •  & Roy Bar-Ziv
  • Article
    | Open Access

    Morphogen gradients can be dynamic and transient yet give rise to stable cellular patterns. Here the authors show that a synthetic morphogen-induced mutual inhibition circuit produces stable boundaries when the spatial average of morphogens falls within the region of bistability.

    • Paul K. Grant
    • , Gregory Szep
    •  & Andrew Phillips
  • Article
    | Open Access

    The extreme oxygen sensitive character of hydrogenases is a longstanding issue for hydrogen production in bacteria. Here, the authors build carboxysome shells in E. coli and incorporate catalytically active hydrogenases and functional partners within the empty shell for the production of hydrogen.

    • Tianpei Li
    • , Qiuyao Jiang
    •  & Lu-Ning Liu
  • Article
    | Open Access

    The trade-off between growth and production affects the application of engineered microbes. Here, the authors take the minimal cut set approach to predict metabolic reactions for elimination to couple metabolite production strongly with growth and achieve high production of indigoidine in Pseudomonas putida.

    • Deepanwita Banerjee
    • , Thomas Eng
    •  & Aindrila Mukhopadhyay
  • Article
    | Open Access

    Tocotrienols are valuable supplementations to α-tocopherol-dominated Vitamin E products. Here, the authors engineer baker’s yeast by combining the heterologous genes from photosynthetic organisms with the endogenous pathway for the production of tocotrienols under cold-shock-triggered temperature control.

    • Bin Shen
    • , Pingping Zhou
    •  & Hongwei Yu
  • Article
    | Open Access

    Addition of fluorine to organic structures is a unique strategy for tuning molecular properties, but approaches to integrate fluorometabolites into the biochemistry of living cells are scarce. Here, the authors develop a fluoride-responsive genetic circuit to enable in vivo biofluorination in engineered Pseudomonas putida.

    • Patricia Calero
    • , Daniel C. Volke
    •  & Pablo I. Nikel
  • Article
    | Open Access

    RNA can be used as a programmable tool for detection of biological analytes. Here the authors use deep neural networks to predict toehold switch functionality in synthetic biology applications.

    • Nicolaas M. Angenent-Mari
    • , Alexander S. Garruss
    •  & James J. Collins
  • Article
    | Open Access

    The design of synthetic biology circuits remains challenging due to poorly understood design rules. Here the authors introduce STORM and NuSpeak, two deep-learning architectures to characterize and optimize toehold switches.

    • Jacqueline A. Valeri
    • , Katherine M. Collins
    •  & Diogo M. Camacho
  • Article
    | Open Access

    The chemical stability of DNA makes complete erasure of DNA-encoded data difficult. Here the authors mix true and false messages, differentiated by whether a truth marker oligo is bound to it, and show that brief exposure to elevated temperatures randomizes the binding of truth markers preventing data recovery.

    • Jangwon Kim
    • , Jin H. Bae
    •  & David Yu Zhang
  • Article
    | Open Access

    In contrast to genetic circuits, here the authors develop protein biocircuits based on proteases. They show these activity-based circuits can execute Boolean logic for programmable drug delivery and perform fuzzy logic to solve a mathematical oracle problem, Learning Parity with Noise.

    • Brandon Alexander Holt
    •  & Gabriel A. Kwong
  • Article
    | Open Access

    Current gene drive strategies are restricted to sexually reproducing species. Here the authors develop a gene drive in herpesviruses that allows the spread of an engineered trait through a viral population.

    • Marius Walter
    •  & Eric Verdin
  • Article
    | Open Access

    In metabolic engineering, mechanistic models require prior metabolism knowledge of the chassis strain, whereas machine learning models need ample training data. Here, the authors combine the mechanistic and machine learning models to improve prediction performance of tryptophan metabolism in baker’s yeast.

    • Jie Zhang
    • , Søren D. Petersen
    •  & Michael K. Jensen
  • Article
    | Open Access

    Synthetic Biology often lacks the predictive power needed for efficient bioengineering. Here the authors present ART, a machine learning and probabilistic predictive tool to guide synthetic biology design in a systematic fashion.

    • Tijana Radivojević
    • , Zak Costello
    •  & Hector Garcia Martin
  • Article
    | Open Access

    Transcriptional biosensors represent powerful tools for the screening of vast strain libraries, but the broad ligand specificity of some transcriptional regulators (TRs) can prohibit such applications. Here authors present the engineering of a LysG-based biosensor with a focused ligand specificity to isolate L-histidine-producing strains.

    • Dennis Della Corte
    • , Hugo L. van Beek
    •  & Jan Marienhagen
  • Article
    | Open Access

    Short hairpin RNAs can be used to modulate and regulate gene expression. Here the authors generate chimeric RNAs that interact with the photoreceptor PAL, allowing for optoribogenetic control of cell physiology.

    • Sebastian Pilsl
    • , Charles Morgan
    •  & Günter Mayer