Synthetic biology articles within Nature Communications

Featured

  • Article
    | Open Access

    Inducible gene expression systems can be used to control the expression of a gene of interest by means of small molecules. Here the authors present CASwitch, a synthetic gene circuit platform enhancing inducible gene expression systems by reducing leakiness and boosting fold induction, for real world applications like gene therapy vector production and biosensors.

    • Giuliano De Carluccio
    • , Virginia Fusco
    •  & Diego di Bernardo
  • Article
    | Open Access

    Several in vitro synthetic enzymatic biosystems (ivSEBs) to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA) have been reported, but suffer from complicated operation procedures, low yields, and/or dependence on costly ATP. Here, the authors report the design of an ATP-free ivSEB for one-pot, high-yield PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate.

    • Xinlei Wei
    • , Xue Yang
    •  & Chun You
  • Perspective
    | Open Access

    Engineering biology is a dynamic field that uses gene editing, synthesis, assembly, and engineering to design new or modified biological systems. Here the authors discuss the policy considerations and interventions needed to support a role for engineering biology in climate change mitigation.

    • Jonathan Symons
    • , Thomas A. Dixon
    •  & Isak S. Pretorius
  • Article
    | Open Access

    The unification of decision-making, communication, and memory would enable the programming of intelligent biotic systems. Here, the authors achieve this goal by engineering E. coli chassis cells with an array of inducible recombinases that mediate diverse genetic programs.

    • Brian D. Huang
    • , Dowan Kim
    •  & Corey J. Wilson
  • Article
    | Open Access

    Production of proteins at scale and affordable cost has been a major need of the biotech sector for the last several decades. Here the authors present a design algorithm called UNILIB for boosting gene expression in eukaryotic cells developed using an oligo-library and machine learning approach, validated in both yeast and mammalian cells using unseen sequences.

    • Inbal Vaknin
    • , Or Willinger
    •  & Roee Amit
  • Article
    | Open Access

    Bispecific antibody architecture is often important for function but rarely optimized. Here, authors present a modular approach to assemble bispecifics in varied formats using a SpyTag/SpyCatcher approach called SpyMask, and build anti-HER2 bispecifics whose activities depend on binder orientation and bispecific geometry.

    • Claudia L. Driscoll
    • , Anthony H. Keeble
    •  & Mark R. Howarth
  • Article
    | Open Access

    Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes. Here the authors present iModulon-based engineering for precise identification of genes for cross-species function transfer to streamline synthetic biology for strain development and biomanufacturing.

    • Donghui Choe
    • , Connor A. Olson
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    Targeting the files containing content-of-interest is a challenge in DNA data storage. Here, the authors develop a CRISPR-powered search engine to quantitatively identify the keyword in files stored in DNA.

    • Jiongyu Zhang
    • , Chengyu Hou
    •  & Changchun Liu
  • Article
    | Open Access

    While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an E. coli strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.

    • Hang Zhou
    • , Yiwen Zhang
    •  & Baixue Lin
  • Article
    | Open Access

    Fungi have the potential to produce sustainable foods for a growing population, but current products are based on a small number of strains with inherent limitations. Here, the authors develop genetic tools for an edible fungus and engineer its nutritional value and sensory appeal for alternative meat applications.

    • Vayu Maini Rekdal
    • , Casper R. B. van der Luijt
    •  & Jay D. Keasling
  • Article
    | Open Access

    Bacteriophages have great potential in both medicine and biotechnology. Here the authors present PHEIGES, a cell-free method for phage genome engineering, synthesis and selection based on T7, which allows direct selection of engineered and mutant phages without compartmentalization.

    • Antoine Levrier
    • , Ioannis Karpathakis
    •  & Vincent Noireaux
  • Article
    | Open Access

    Gene expression is inherently dynamic, due to complex regulation and stochastic biochemical events. Here the authors train a deep neural network to predict and dynamically control gene expression in thousands of individual bacteria in real-time which they then apply to control antibiotic resistance and study single-cell survival dynamics.

    • Jean-Baptiste Lugagne
    • , Caroline M. Blassick
    •  & Mary J. Dunlop
  • Article
    | Open Access

    Engineered biosensing bacteria can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. Here the authors present a robust biocontainment assisted by Cas9 and an engineered gene expression control combined in a genetically engineered human commensal bacterium that successfully functioned in a mouse intestinal tract as well as cell culture condition.

    • Naoki Hayashi
    • , Yong Lai
    •  & Timothy K. Lu
  • Article
    | Open Access

    Amaryllidaceae alkaloids, such as the Alzheimer’s medication galantamine, are currently extracted from low-yielding daffodils. Here, authors pair biosensor-assisted screening with machine learning-guided protein design to rapidly engineer an improved Amaryllidaceae enzyme in a microbial host.

    • Simon d’Oelsnitz
    • , Daniel J. Diaz
    •  & Andrew D. Ellington
  • Article
    | Open Access

    The soil microbiome communicates with plant roots using a chemical language. Here, using p-coumaroyl-homoserine lactone as the synthetic communication signal, the authors demonstrate programmable microbe-to-plant communication from the sender in the soil bacteria to a receiver in the plant.

    • Alice Boo
    • , Tyler Toth
    •  & Christopher A. Voigt
  • Article
    | Open Access

    Recent protein design methods rely on large neural networks, yet it is unclear which dependencies are critical for determining function. Here, authors show that learning the per residue mutation preferences, without considering interactions, enables design of functional and diverse protein variants.

    • David Ding
    • , Ada Y. Shaw
    •  & Debora S. Marks
  • Article
    | Open Access

    Interfacing living systems with electronics for biosensing and biocomputing applications is challenging. Here, Gao et al. present hybrid transistors with electroactive bacteria capable of extracellular electron transfer, enabling transduction of biological computations to electrical readouts.

    • Yang Gao
    • , Yuchen Zhou
    •  & Benjamin K. Keitz
  • Review Article
    | Open Access

    Engineering the form and function of root systems and their associated microbiota could provide a means to mitigate adverse climate-driven effects. Here, the authors review the recent developments in plant and rhizobacterial synthetic biology and highlight engineering targets for applications in root systems and rhizosphere.

    • Carin J. Ragland
    • , Kevin Y. Shih
    •  & José R. Dinneny
  • Article
    | Open Access

    Site-specific recombinases such as the Cre-LoxP system are routinely used for genome engineering in both prokaryotes and eukaryotes. Here the authors develop 63 symmetrical LoxP variants and test 1192 pairwise combinations to determine their cross-reactivity and specificity upon Cre activation.

    • Charlotte Cautereels
    • , Jolien Smets
    •  & Kevin J. Verstrepen
  • Article
    | Open Access

    Descriptive data in biomedical research are expanding rapidly, but functional validation methods lag behind. Here, authors present Logical Synthetic cis-regulatory DNA, a framework to design reporters that mark cellular states and pathways, showcasing its applicability to complex phenotypic states.

    • Carlos Company
    • , Matthias Jürgen Schmitt
    •  & Gaetano Gargiulo
  • Article
    | Open Access

    CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. Here the authors show an anti-drive mosquito strain that prevents the spread and collapse of a population suppression gene drive in laboratory Anopheles mosquito large cage trials in complex ecological and behavioral conditions.

    • Rocco D’Amato
    • , Chrysanthi Taxiarchi
    •  & Ruth Müller
  • Article
    | Open Access

    Achieving genetic circuits on single DNA molecules could have varied applications. Here, authors observed proteins emerging from single DNA molecules through coupled transcription-translation complexes, and show that nascent proteins lingered on DNA, regulating cascaded reactions on the same DNA and allowing the design of a pulsatile genetic circuit.

    • Ferdinand Greiss
    • , Nicolas Lardon
    •  & Roy Bar-Ziv
  • Article
    | Open Access

    Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. Here the authors present an engineered yeast strain with 83 sparsely distributed loxPsym sites across the genome can genrerate large-scale genomic rearrangements, which benefits cell fitness under stress and boosts the SCRaMbLE system when combined with synthetic chromosomes.

    • Li Cheng
    • , Shijun Zhao
    •  & Junbiao Dai
  • Article
    | Open Access

    Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Here the authors find that a CRISPR/Cas9 based split gene drive in Aedes aegypti could successfully bias inheritance up to 89% over successive generations in a multi-cage trial with further deep sequencing suggesting that the multiplexing design could mitigate resistance allele formation.

    • Michelle A. E. Anderson
    • , Estela Gonzalez
    •  & Luke Alphey
  • Article
    | Open Access

    No consensus exists on the computationally tractable use of dynamic models for strain design. To tackle this, the authors report a framework, nonlinear-dynamic-model-assisted rational metabolic engineering design, for efficiently designing robust, artificially engineered cellular organisms.

    • Bharath Narayanan
    • , Daniel Weilandt
    •  & Vassily Hatzimanikatis
  • Comment
    | Open Access

    While the research community continues to develop novel proposals for intrinsic biocontainment of genetically engineered organisms, translation to real-world deployment faces several challenges.

    • Dalton R. George
    • , Mark Danciu
    •  & Emma K. Frow
  • Article
    | Open Access

    Homing-based gene drives are novel interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here the authors demonstrate the feasibility of a gene drive approach for the genetic control of the agricultural pest, the medfly, based on complete female-to-male sex conversion.

    • Angela Meccariello
    • , Shibo Hou
    •  & Nikolai Windbichler
  • Article
    | Open Access

    Xanthohumol is a prenylated flavonoid produced by hops and is an important flavor substance in beer. Here, the authors engineer brewing yeast for the de novo biosynthesis of xanthohumol from glucose by balancing the three parallel biosynthetic pathways.

    • Shan Yang
    • , Ruibing Chen
    •  & Yongjin J. Zhou
  • Article
    | Open Access

    Coacervate droplets have potential as components for cell-like materials, but are limited by complex molecular structure and control of the internal microenvironment. Here, the authors report stable dipeptide-based coacervates with a microenvironment for the encapsulation of hydrophobic species.

    • Shoupeng Cao
    • , Tsvetomir Ivanov
    •  & Lucas Caire da Silva
  • Article
    | Open Access

    Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here the authors develop a high throughput non-invasive method for tracking suspension and adhesion mammalian cell growth based on plate reader measures to characterize engineered cell lines.

    • Alice Grob
    • , Chiara Enrico Bena
    •  & Francesca Ceroni
  • Article
    | Open Access

    Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.

    • Alessandro L. V. Coradini
    • , Christopher Ne Ville
    •  & Ian M. Ehrenreich
  • Review Article
    | Open Access

    As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. In this review, the authors outline design strategies for the DNA, RNA, and protein-level circuits and the hybrid “multi-level” circuits.

    • Yuanli Gao
    • , Lei Wang
    •  & Baojun Wang
  • Article
    | Open Access

    Prediction of enzyme kinetic parameters is essential for designing and optimising enzymes for various biotechnological and industrial applications. Here, authors presented a prediction framework (UniKP), which improves the accuracy of predictions for three enzyme kinetic parameters.

    • Han Yu
    • , Huaxiang Deng
    •  & Xiaozhou Luo
  • Article
    | Open Access

    Microbial rhodopsins are major contributors to global light harvesting on Earth, but their role in carbon fixation is unclear. Here, the authors construct an artificial photosynthesis system by combining rhodopsin with an extracellular electron uptake mechanism for photoelectrosynthetic CO2 fixation in Ralstonia eutropha.

    • Weiming Tu
    • , Jiabao Xu
    •  & Wei E. Huang
  • Article
    | Open Access

    Membraneless liquid compartments based on phase-separating biopolymers have been observed in diverse cell types and attributed to weak multivalent interactions predominantly based on intrinsically disordered domains. Here the authors design protein liquid condensates from tunable concatenated coiled-coil dimer modules, unraveling the principles for coexisting condensates, chemical regulation, formation from either one or two polypeptide components in mammalian cells.

    • Maruša Ramšak
    • , Dominique A. Ramirez
    •  & Roman Jerala
  • Article
    | Open Access

    In Saccharomyces cerevisiae, the left arm of chromosome XII only requires 12 genes to maintain cell viability, whereas 25 genes are needed for robust fitness. Here the authors demonstrate that the entire arm can be replaced by a neochromosome with completely artificial sequences.

    • Shuangying Jiang
    • , Zhouqing Luo
    •  & Junbiao Dai
  • Article
    | Open Access

    Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.

    • Tatsat Banerjee
    • , Satomi Matsuoka
    •  & Pablo A. Iglesias
  • Article
    | Open Access

    The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.

    • Maximilian A. Funk
    • , Judith Leitner
    •  & Peter Steinberger
  • Article
    | Open Access

    Chemical inducer of dimerization (CID) modules can be used to effectively control biological processes; however, CID modules have been explored primarily in engineering cells for in vitro applications using inducers that have limited clinical utility. Here, the authors identify a CID module with favorable properties to enable rapid translation from in vitro applications to potential use in humans.

    • Stacey E. Chin
    • , Christina Schindler
    •  & Natalie J. Tigue