Synthetic biology articles within Nature Communications

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  • Article
    | Open Access

    Multi-enzymatic cascades benefit from precise nanometric organization but achieving this using available scaffolds is challenging. Here the authors present strategy for organizing multienzymatic systems using a protein scaffold based on TRAP domains, and demonstrate improved catalytic output.

    • Alba Ledesma-Fernandez
    • , Susana Velasco-Lozano
    •  & Aitziber L. Cortajarena

  • Article
    | Open Access

    Genetic modules are sensitive to changes in their context and to environmental perturbations. Here, the authors develop a genetic optimizer based on common synthetic biology parts to ensure optimal and robust cellular performance in diverse contexts.

    • Andras Gyorgy
    • , Amor Menezes
    •  & Murat Arcak

  • Article
    | Open Access

    Sustained drug delivery is critical for patient adherence to chronic disease treatments. Here the authors apply machine learning to engineer multifunctional peptides with high melanin binding, high cell-penetration, and low cytotoxicity, enhancing the duration and efficacy of peptide-drug conjugates for sustained ocular delivery.

    • Henry T. Hsueh
    • , Renee Ti Chou
    •  & Laura M. Ensign

  • Article
    | Open Access

    Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. Here the authors combine construction of over 20 synthetic gene regulatory networks with mathematical modeling to exemplify how gene regulatory networks provide robustness in face of mutations while enabling transitions to innovative phenotypes.

    • Javier Santos-Moreno
    • , Eve Tasiudi
    •  & Yolanda Schaerli

  • Article
    | Open Access

    Cell-free genetically encoded biosensors have been developed to detect small molecules and nucleic acids, but they have yet to be reliably engineered to detect proteins. Here the authors develop an automated platform to convert protein-binding RNA aptamers into riboswitch sensors that operate within low-cost cell-free assays.

    • Grace E. Vezeau
    • , Lipika R. Gadila
    •  & Howard M. Salis

  • Article
    | Open Access

    Enabling high-bandwidth communication between cells is a prerequisite for engineering multicellular consortia that can perform sophisticated computations and functions. Here, the authors design a framework for addressable and adaptable DNA-based communication and implement it using plasmid conjugation in a E. coli population.

    • John P. Marken
    •  & Richard M. Murray

  • Article
    | Open Access

    Omicron BA.1 is attenuated in infection models though the precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging. Here the authors present pGLUE, a plasmid-based viral genome assembly and rescue strategy, to systematically characterize Omicron mutations and show that Omicron NSP6 has weakened lipid flow to replication organelles and reduced viral RNA replication.

    • Taha Y. Taha
    • , Irene P. Chen
    •  & Melanie Ott

  • Article
    | Open Access

    Biological computation is becoming a viable and fast-growing alternative to traditional electronic computing. Here the authors present Trumpet, which uses DNA and enzymes to build logic gate circuits with amplified fluorescent readout.

    • Judee A. Sharon
    • , Chelsea Dasrath
    •  & Katarzyna P. Adamala

  • Article
    | Open Access

    The scarcity of qualified RNA-binding proteins hinders the development of artificial translational regulators and synthetic gene circuits. Here, the authors repurposed CRISPR-Cas proteins as translational regulators to build synthetic circuits.

    • Shunsuke Kawasaki
    • , Hiroki Ono
    •  & Hirohide Saito

  • Article
    | Open Access

    Tools for the spatiotemporal control of protein abundance are valuable in studying diverse complex biological processes. Here, authors engineered a protein tag which is stabilized upon light induction but which quickly degrades the protein of interest in the dark, demonstrating control of protein stability in yeast and zebrafish.

    • Miaowei Mao
    • , Yajie Qian
    •  & Yi Yang

  • Article
    | Open Access

    DNA is a universal and programmable signal of living organisms. Here, the authors develop cell-based DNA sensors by engineering the naturally competent bacterium Bacillus subtilis to detect specific DNA sequences in the environment.

    • Yu-Yu Cheng
    • , Zhengyi Chen
    •  & Ophelia S. Venturelli

  • Review Article
    | Open Access

    Naturally evolved genomes tend to be unnecessarily large and redundant, and are not optimised for biotechnological or research applications. In this review, the authors explore genome minimization and re-functionalisation approaches, and discuss their potential for industrial applications.

    • Xin Xu
    • , Felix Meier
    •  & Thomas C. Williams

  • Article
    | Open Access

    New protein assemblies can be introduced through the fusion of selected proteins with di/oligomerization domains, which interact specifically with their partners but not with other cellular proteins. Here the authors demonstrate that a single four-helical bundle protein can be segmented into several different parts, defining up to four interacting molecules for enzyme reconstitution, gene expression, or CAR-T cell regulation.

    • Estera Merljak
    • , Benjamin Malovrh
    •  & Roman Jerala

  • Article
    | Open Access

    Synthetic circuits that can record in vivo signaling networks is critical in elucidating developmental process. Here, the authors describe the engineering and application of synthetic in vivo recorders with different promoters that can drive spatiotemporally-specific integrase switching during lateral root initiation.

    • Sarah Guiziou
    • , Cassandra J. Maranas
    •  & Jennifer L. Nemhauser

  • Article
    | Open Access

    Transmembrane signaling is the core adaptation in nature that allows cells to communicate. Here, the authors engineer signaling through the lipid bilayer using chemical, synthetic receptors for their use in the design of artificial cells.

    • Ane Bretschneider Søgaard
    • , Andreas Bøtker Pedersen
    •  & Alexander N. Zelikin

  • Article
    | Open Access

    Resolving the stoichiometry of membrane protein interactions is challenging but is vital to understand cell signalling. Using lipid-bound DNA receptors as a model for membrane proteins, the authors present a platform to achieve stoichiometric, spatial and temporal control over their interactions.

    • Vishal Maingi
    • , Zhao Zhang
    •  & Paul W. K. Rothemund

  • Article
    | Open Access

    Context-dependency of mammalian transcriptional elements has hindered the quantitative investigation of multigene expression stoichiometry and its biological functions. Here the authors present a host-orthogonal transcriptional system that drives tunable gene expression in mammalian cells, enabling predictive fine-tuning of multi-gene expression stoichiometry and the production optimization of virus-like particles from mammalian cells.

    • Chenrui Qin
    • , Yanhui Xiang
    •  & Chunbo Lou

  • Article
    | Open Access

    Non-equilibrium conditions at heated water-air interfaces can model Hadean microenvironments. Here, the authors show that such conditions enable one-pot synthesis, strand release and folding of functional RNAs similar to modern biological systems.

    • Annalena Salditt
    • , Leonie Karr
    •  & Hannes Mutschler

  • Article
    | Open Access

    Nucleic acid sensing involving CRISPR technologies is powerful but has certain limitations, such as PAM sequence requirements and limited multiplexing. Here, authors report a CRISPR-based barcoding technology which enables multiple outputs from any target sequence, based on cis- and trans-cleavage.

    • Margot Karlikow
    • , Evan Amalfitano
    •  & Keith Pardee

  • Article
    | Open Access

    Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. Here the authors engineer programmable RNA sensors, DART VADARs, in which ADARs autocatalytically convert target hybridization into a translational output, thus amplifying editing by endogenous ADAR via positive feedback and conferring high dynamic range and a small genetic footprint.

    • Raphaël V. Gayet
    • , Katherine Ilia
    •  & James J. Collins

  • Article
    | Open Access

    There is a low efficiency of A-to-G base conversion in at specific positions using base editors. Here the authors fuse ABE8e with the Rad51 DNA-binding domain to generate a hyperactive ABE allowing improved A-to-G editing efficiency at the region proximal to the PAM and improved simultaneous A/C conversion efficiency.

    • Niannian Xue
    • , Xu Liu
    •  & Xiaohui Zhang

  • Article
    | Open Access

    Antibiotics are a key control mechanism for synthetic biology and microbiology. Here, using an optogenetic recombinase, the authors develop genetic constructs where antibiotic resistance levels in bacteria can be controlled using light.

    • Michael B. Sheets
    • , Nathan Tague
    •  & Mary J. Dunlop

  • Article
    | Open Access

    While the ribosome has been harnessed for synthetic biology, designing ribosomes has remained challenging. Here, the authors demonstrate a community science approach for rational design of ribosomes with beneficial properties.

    • Antje Krüger
    • , Andrew M. Watkins
    •  & Michael C. Jewett

  • Article
    | Open Access

    The treatment of snakebite envenoming is currently suboptimal. Existing antivenoms often lack efficacy and may cause adverse reactions. Here, the authors derive, develop, and demonstrate the utility of toxin-specific broadly-neutralizing human monoclonal antibodies with established reactivity across related venom toxins from different snake species and show efficacy in rodent models.

    • Line Ledsgaard
    • , Jack Wade
    •  & Aneesh Karatt-Vellatt

  • Article
    | Open Access

    Genome editing in bacteria normally requires efficient recombination and high transformation efficiencies, which often isn’t. Here the authors report that systematically attenuating DNA targeting activity enables RecA-mediated repair in different bacteria, allowing chromosomal cleavage to drive editing.

    • Daphne Collias
    • , Elena Vialetto
    •  & Chase L. Beisel

  • Article
    | Open Access

    RNA provides a unique readout of a cell’s identity, physiologic status, and phenotype. Here the authors deliver an RNA sensing system that can use the information contained within cellular RNA to selectively control the activity of genetic programs.

    • Lauren Gambill
    • , August Staubus
    •  & James Chappell

  • Article
    | Open Access

    CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

    • Michelle A. E. Anderson
    • , Estela Gonzalez
    •  & Luke Alphey

  • Article
    | Open Access

    CRISPR-based gene-drives can carry the Cas9 and guide RNA (gRNA) components in a single-linked cassette or in separate elements inserted into different genomic loci. Here the authors genetically transform and compare full versus split drives, with the former performing less efficiently than predicted.

    • Gerard Terradas
    • , Jared B. Bennett
    •  & Ethan Bier

  • Article
    | Open Access

    Phase separation provides intracellular organisation via membraneless entities called biomolecular condensates. Here, the authors show that short, cationic peptide tags can drive biomolecular condensation of engineered proteins in E. coli through associative interactions with RNA.

    • Vivian Yeong
    • , Jou-wen Wang
    •  & Allie C. Obermeyer

  • Article
    | Open Access

    Synthetic biology often involves engineering microbial strains to express high-value proteins. Here the authors build deep learning predictors of protein expression from sequence that deliver accurate models with fewer data than previously assumed, helping to lower costs of model-driven strain design.

    • Evangelos-Marios Nikolados
    • , Arin Wongprommoon
    •  & Diego A. Oyarzún

  • Article
    | Open Access

    The biosynthetic pathway of type II ganoderic acids (GAs) in Ganoderma lucidum, a traditional medicinal mushroom, is unknown. Here, the authors assemble the genome of type II GAs accumulating accession, identify CYPs involving in type II GAs biosynthesis, and achieve their production in engineered baker’s yeast.

    • Wei Yuan
    • , Chenjian Jiang
    •  & Han Xiao

  • Article
    | Open Access

    The development of broad-spectrum antivirals is an important part of pandemic preparedness and response. Here the authors present ALICE, synthetic biology designer immune-like cells that act as a sense-and-destroy antiviral system can detect viruses from seven different genera, mimicking the human innate immune system.

    • Yidan Wang
    • , Ying Xu
    •  & Haifeng Ye

  • Article
    | Open Access

    Identifying the designers of engineered biological sequences would help promote biotechnological innovation while holding designers accountable. Here the authors present the winners of a 2020 data-science competition which improved on previous attempts to attribute plasmid sequences.

    • Oliver M. Crook
    • , Kelsey Lane Warmbrod
    •  & William J. Bradshaw

  • Article
    | Open Access

    Artificial receptors targeted to the secretory pathway often fail to exhibit the expected activity due to post-translational modifications and/or improper folding. Here, the authors engineer diverse synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum, or on the plasma membrane through orientation adjustment of the receptor parts and by elimination of dysfunctional PTMs sites.

    • Mohamed Mahameed
    • , Pengli Wang
    •  & Martin Fussenegger

  • Article
    | Open Access

    Engineering enzymes to accept noncanonical cofactor biomimetics is difficult. Here, the authors establish a self-sufficient growth selection method and demonstrate its application in engineering the Lactobacillus pentosus NADH oxidase to efficiently recycle reduced nicotinamide mononucleotide (NMNH).

    • Edward King
    • , Sarah Maxel
    •  & Han Li

  • Article
    | Open Access

    Protein phosphorylation is a ubiquitous post-translational modification used to regulate cellular processes and proteome architecture by modulating protein-protein interactions. Here the authors optimize genetically encoded phosphothreonine to study the regulation of CHK2 kinase using large-scale DNA arrays that enable phosphoproteome expression techniques to identify sitespecific overlap between CHK2 substrates and 14-3-3 interactions.

    • Jack M. Moen
    • , Kyle Mohler
    •  & Jesse Rinehart

  • Article
    | Open Access

    Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here the authors present a tunable, modular, and portable feedforward controller that allows dynamic modulation of a genes expression to possibly high-levels without substantially affecting growth rate.

    • Carlos Barajas
    • , Hsin-Ho Huang
    •  & Domitilla Del Vecchio

  • Article
    | Open Access

    Reductive stress, reflected by the elevated intracellular NADH/NAD+ ratio, is associated with multiple human diseases. Here, the authors develop a genetic tool to manipulate the ratios of cellular NADH/NAD+ and NADPH/NADP+, and identify purine biosynthesis as an NADH-sensing pathway to mediate reductive stress.

    • Ronghui Yang
    • , Chuanzhen Yang
    •  & Binghui Li

  • Article
    | Open Access

    RNA viruses have been responsible for large-scale epidemics and pandemics throughout the last few centuries. Here, the authors show the design, synthesis and screening of artificial RNA endonuclease XNAzymes capable of cleaving genomic SARS-CoV-2 RNA and self-assembling into enzymatic nanostructures inhibiting cellular viral replication.

    • Pehuén Pereyra Gerber
    • , Maria J. Donde
    •  & Alexander I. Taylor

  • Article
    | Open Access

    The ability to externally control gene expression has been important for all areas of biological research, especially for synthetic biology. Here the authors present plasmid TULIP which offers DNA copy number control via chemical induction to accelerate the design, prototyping, and reuse of gene circuits in diverse contexts.

    • Shivang Hina-Nilesh Joshi
    • , Chentao Yong
    •  & Andras Gyorgy

  • Article
    | Open Access

    A challenge in synthetic biology is the empirical characterisation of genetic parts. Here the authors present FPCountR, a validated method and accompanying R package that enables the precise quantification of fluorescent protein reporters per bacterial cell to be enumerated in ‘proteins per cell’ or nanomolar units without requiring protein purification.

    • Eszter Csibra
    •  & Guy-Bart Stan

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