Synthetic biology articles within Nature Communications

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  • 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
  • Article
    | Open Access

    Engineering ammonium excretion diazotrophs suffers from severe penalties to the bacteria. Here, the authors utilize a thermo-sensitive glutamine synthetase-based regulatory switch that permits diurnal changes in diazotrophic lifestyle, coincident with seasonal temperatures for cereal cultivation.

    • Yuqian Tang
    • , Debin Qin
    •  & Yi-Ping Wang
  • Article
    | Open Access

    Sufficient supply of sulfonate group donor is critical to biomanufacturing of the sulfate containing compounds. Here, the authors engineer two sulfonate group donor regeneration systems, including 3'-phosphoadenosine-5'-phosphosulfate and the newly discovered 5'-phosphosulfate, to boost biosynthesis of sulfated compounds.

    • Ruirui Xu
    • , Weijao Zhang
    •  & Zhen Kang
  • Article
    | Open Access

    Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.

    • Amir Pandi
    • , David Adam
    •  & Tobias J. Erb
  • Article
    | Open Access

    The rational design and implementation of synthetic mammalian communication systems can unravel fundamental design principles of cell communication circuits and offer a framework for engineering of designer cell consortia with potential applications in cell therapeutics. Here the authors present a synthetic communication platform in mammalian cells based on diffusible dipeptide ligands and synthetic receptors, that is by design highly orthogonal, scalable, and programmable.

    • Anna-Maria Makri Pistikou
    • , Glenn A. O. Cremers
    •  & Tom F. A. de Greef
  • Perspective
    | Open Access

    The utilization of one-carbon assimilation pathways for bioproduction represents a promising direction towards a more sustainable bio-based economy. Here, the authors compare the thermodynamic efficiencies and energy demand of C1-assimilation pathways and discuss their implementation for energy, material, and food production.

    • Simone Bachleitner
    • , Özge Ata
    •  & Diethard Mattanovich
  • Article
    | Open Access

    Genetic code expansion (GCE) is a protein engineering tool that enables programmed and site-specific installation of noncanonical amino acids into proteins. Here, authors show that cellular stress remodelling boosts GCE in mammalian cells including GCE realized by orthogonally translating organelles.

    • Mikhail E. Sushkin
    • , Christine Koehler
    •  & Edward A. Lemke
  • Article
    | Open Access

    Many diseases are driven by the insufficient expression of critical genes, but few technologies are capable of rescuing these endogenous protein levels. Here, Cao et al. present an RNA-based technology that boosts protein production from endogenous mRNAs by upregulating their translation.

    • Yang Cao
    • , Huachun Liu
    •  & Bryan C. Dickinson
  • Perspective
    | Open Access

    Using one carbon (C1) molecules as primary feedstock for bioproduction holds great potential for a circular and carbon neutral economy. Here, the authors discuss the potential of merging knowledge gained from natural and synthetic C1-trophic organisms to expedite the development of efficient C1-based biomanufacturing.

    • Enrico Orsi
    • , Pablo Ivan Nikel
    •  & Stefano Donati
  • Article
    | Open Access

    Synthetic gene networks in mammalian cells are currently limited to either transcription factors or RNA regulators. Here, the authors develop a regulatory approach based on circular single-stranded DNA, which can be used as a conformationally switchable genetic vector in mammalian cells.

    • Linlin Tang
    • , Zhijin Tian
    •  & Jie Song
  • Article
    | Open Access

    Exogenous control of genes in vivo is important. Here the authors report a system that can be inducibly activated through thermal energy produced by ultrasound absorption and use this to control induction of gene activation and base editing: they apply this in cell lines and in a mouse model.

    • Pei Liu
    • , Josquin Foiret
    •  & Lei S. Qi
  • Article
    | Open Access

    Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid provides a powerful strategy to restrict unwanted propagation of genetically modified organisms in open environments and potentially prevent industrial espionage. Here the authors establish a general framework for the creation and optimization of synthetic auxotrophs in yeast.

    • Tiantian Chang
    • , Weichao Ding
    •  & Xian Fu
  • Article
    | Open Access

    DNA is an alternative to data storage materials for its durability, density, and energetics. Here the authors demonstrate the storage of digital information on DNA molecules using base-editing.

    • Afsaneh Sadremomtaz
    • , Robert F. Glass
    •  & Reza Zadegan
  • Article
    | Open Access

    One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. Here the authors describe a Cas12a gene drive system whose activity can be finetuned in a temperature-dependent manner.

    • Sara Sanz Juste
    • , Emily M. Okamoto
    •  & Víctor López Del Amo
  • Article
    | Open Access

    Designing promoters with desired properties is crucial in synthetic biology. Here, authors introduce DeepSEED, an AI-aided flanking sequence optimisation framework which combines expert knowledge with deep learning techniques to efficiently design promoters in both eukaryotic and prokaryotic cells.

    • Pengcheng Zhang
    • , Haochen Wang
    •  & Xiaowo Wang
  • Article
    | Open Access

    Generating and controlling cell collective behavior is important for synthetic biology and bioproduction. Here, the authors show the diversification dynamic and the fitness cost associated with cell switching are coupled in yeast and bacteria, and demonstrate the feasibility of controlling diversification regimes.

    • Lucas Henrion
    • , Juan Andres Martinez
    •  & Frank Delvigne
  • Article
    | Open Access

    Archiving data in synthetic DNA offers unprecedented storage density and longevity. To understand how experimental choices affect the integrity of digital data stored in DNA, the authors study the evolution of errors and bias and with a digital twin they supply tools for experimental planning and design of error-correcing codes.

    • Andreas L. Gimpel
    • , Wendelin J. Stark
    •  & Robert N. Grass
  • Article
    | Open Access

    Plastic pollution is rapidly increasing worldwide, causing adverse impacts on the environment, wildlife and human health. Here the authors present a synthetic microbial consortium that efficiently degrades polyethylene terephthalate hydrolysate and upcycles it to desired chemicals through cellular division of labor.

    • Teng Bao
    • , Yuanchao Qian
    •  & Ting Lu
  • Article
    | Open Access

    In metabolic engineering, releasing of carbon in the form of CO2 leads to significant decrease of atomic economy. Here, the authors construct a carbon-conserving pathway, which converts glucose into acetyl phosphate without carbon loss, with oscillatory system to improve production of multiple target compounds.

    • Likun Guo
    • , Min Liu
    •  & Guang Zhao
  • Article
    | Open Access

    Memory is a basic tenet of intelligent biological systems. Here the authors engineered a programmable and expandable iteration of recombinase-based synthetic memory (interception) that functions post-translation, resulting in faster recombination.

    • Andrew E. Short
    • , Dowan Kim
    •  & Corey J. Wilson
  • Article
    | Open Access

    Genetic code expansion is limited by the degeneracy of the 61 sense codons which encode for only 20 amino acids. Here, the authors show that by combining hyperaccurate ribosomes and in vitro transcribed tRNAs, dramatic and extensive breaking of sense codon degeneracy can be achieved.

    • Clinton A. L. McFeely
    • , Bipasana Shakya
    •  & Matthew C. T. Hartman
  • Article
    | Open Access

    Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signalling pathways. Here the authors present a programmable conformational cooperativity strategy to construct the oligo-protein signal transduction platform for logic operations and gene regulations which can be cooperatively regulated by conformational signals.

    • Yuan Liang
    • , Yunkai Qie
    •  & Cheng Zhang
  • Article
    | Open Access

    Engineered living materials (ELMs) are emerging as a field at the intersection of materials science and synthetic biology. Here, the authors describe a photosynthetic ELM composed of genetically engineered cyanobacteria in a hydrogel matrix, capable of bioremediation and inducible cell death.

    • Debika Datta
    • , Elliot L. Weiss
    •  & Jonathan K. Pokorski
  • Article
    | Open Access

    Protein-protein interactions (PPIs) are crucial for biological functions and have applications ranging from drug design to synthetic cell circuits. Here the authors develop an assay and computational methods to identify more orthogonal coiled-coil pairs, critical for biological processes and drug design.

    • W. Clifford Boldridge
    • , Ajasja Ljubetič
    •  & Sriram Kosuri
  • Article
    | Open Access

    Mature fields of engineering use physics-based models to design systems that work reliably the first time. Here the authors show how a similar approach can be used to design and build a cellular-scale system, protein synthesis, from scratch.

    • Akshay J. Maheshwari
    • , Jonathan Calles
    •  & Drew Endy
  • Article
    | Open Access

    Plant-derived phenylpropanoids have diverse industrial applications ranging from flavours and fragrances to polymers and pharmaceuticals. Here the authors present a tripartite microbial coculture with mix-and-match flexibility and had improved stability within an engineered living material platform for de novo production of several plant-derived phenylpropanoids.

    • Sierra M. Brooks
    • , Celeste Marsan
    •  & Hal S. Alper
  • Article
    | Open Access

    The ability to independently control the expression of different genes is important for quantitative biology. Here, the authors report kinetic parameters, noise scaling, impact on growth, and the fundamental leakiness of a wide range of inducible transcriptional systems, including a new, highly light sensitive LOV-transcription factor.

    • Vojislav Gligorovski
    • , Ahmad Sadeghi
    •  & Sahand Jamal Rahi
  • Article
    | Open Access

    Endonucleases play crucial roles in various biological processes but endonucleases that target small non-coding RNAs have not been reported. Here, the authors combined the metal binding non-canonical amino acid BpyAla and a high affinity binder to engineer a catalyst that degrades small non-coding RNAs.

    • Noreen Ahmed
    • , Nadine Ahmed
    •  & John Paul Pezacki
  • Article
    | Open Access

    Resource competition can be the cause of unintended coupling between co-expressed genetic constructs. Here the authors quantify the resource load imposed by different mammalian genetic components to identify construct designs with increased performance and reduced resource footprint.

    • Roberto Di Blasi
    • , Mara Pisani
    •  & Francesca Ceroni
  • Article
    | Open Access

    Natural proteins exhibit rich structural diversity based on the folds of an invariably linear chain. Here the authors design a single-domain GFP catenane as the counterpart of conventional linear GFP with enhanced thermal resilience and to provide a robust scaffold for making fusion protein catenanes.

    • Zhiyu Qu
    • , Jing Fang
    •  & Wen-Bin Zhang
  • Article
    | Open Access

    Predicting the evolution of engineered cell populations is an increasingly popular topic in biotechnology. Here the authors build a model that explores evolution in engineered cell populations which can generate hypotheses that could lead to important insights into strategies for assessing and mitigating the effects of evolution.

    • Duncan Ingram
    •  & Guy-Bart Stan
  • Article
    | Open Access

    In vivo mutagenesis allows improving cell factories through directed evolution. Here, the authors present CoMuTER, a tool for targetable random mutagenesis of complete biosynthetic pathways using a Cas3 enzyme fused to a cytidine deaminase.

    • Anna Zimmermann
    • , Julian E. Prieto-Vivas
    •  & Kevin J. Verstrepen
  • Article
    | Open Access

    NADP(H) is a crucial cofactor, acting as a reducing agent in numerous pathways in living organisms. Here the authors report a ratiometric biosensor named NERNST, which can be used to estimate the NADP(H) redox status in bacterial, plant and animal cells and organelles.

    • Pamela E. Molinari
    • , Adriana R. Krapp
    •  & Matias D. Zurbriggen
  • Article
    | Open Access

    Ultrasensitive, real-time profiling of bio-analytes is a prerequisite for precision medicine. Here, the authors present a versatile bio-electronic interface (VIBE) to sense signaling cascade-guided receptor-ligand interactions and show that it can detect hormone levels in blood samples and differentiate individual metabolic conditions.

    • Preetam Guha Ray
    • , Debasis Maity
    •  & Martin Fussenegger