Molecular engineering articles within Nature Communications

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  • Article
    | Open Access

    The SpyTag/SpyCatcher protein ligation technology is valuable in many applications, but few methods exist for controlling reactivity. Here the authors report a method for controlling SpyCatcher activity via S-thiolation of engineered cysteines, demonstrating the value of their technology for the rapid generation of bispecific antibodies.

    • Christian Hentrich
    • , Mateusz Putyrski
    •  & Francisco Ylera
  • Article
    | Open Access

    Targeted degradation has emerged as a powerful therapeutic modality. In this study, the authors develop a lipid-based platform to deliver recombinant bioPROTACs into cells for targeted protein degradation, providing a platform for efficient intracellular degradation of proteins that may elude chemical inhibition.

    • Alexander Chan
    • , Rebecca M. Haley
    •  & Andrew Tsourkas
  • Article
    | Open Access

    ATP dynamics influence bioproduction yet are largely unexplored in this context. Here, authors unravel ATP dynamics across various conditions, identify carbon sources which boost ATP levels and bioproduction, and uncover metabolic bottlenecks, shedding light on how ATP dynamics can be used to enhance bioproduction.

    • Xinyue Mu
    • , Trent D. Evans
    •  & Fuzhong Zhang
  • Article
    | Open Access

    Technologies that generate precise combinatorial genome modifications are well suited to dissect the polygenic basis of complex phenotypes and engineer synthetic genomes. Here the authors systematically optimize eMAGE for enhanced editing efficiency and editing distance and apply these advances to identify genetic factors of nuclear hormone dysfunction.

    • Peter N. Ciaccia
    • , Zhuobin Liang
    •  & Farren J. Isaacs
  • Article
    | Open Access

    Engineered sex ratio distorters have been proposed as a powerful component of genetic control strategies designed to suppress harmful insect pests. Here the authors show that sex ratio distorters behave in unexpected ways in malaria mosquitoes, offering new paths for genetic pest control by targeting sex ratios.

    • Daniella An Haber
    • , Yael Arien
    •  & Philippos Aris Papathanos
  • Article
    | Open Access

    Synthetic biology applications require finely tuned gene expression, often mediated by synthetic transcription factors. Here the authors validate two plant-derived proteins, FHY1 and FHL, acting as transactivators in mammalian cells for orthogonal, modular, and tunable control of gene transcription by forming a photosensing transcriptional regulation complex with PhyA.

    • Deqiang Kong
    • , Yang Zhou
    •  & Haifeng Ye
  • Perspective
    | Open Access

    Microbial degradation and biosynthesis of fluorinated compounds is a field of increasing importance, but is hampered by the significant toxicity of fluoride. Here authors discuss emerging ideas on microbial defluorination/fluorination and fluoride resistance mechanisms, providing guidance on how this knowledge can guide future bioengineering approaches.

    • Randy B. Stockbridge
    •  & Lawrence P. Wackett
  • Article
    | Open Access

    Soluble methane monooxygenase (sMMO) is a potentially value biocatalyst, but production of active recombinant sMMO is very challenging. Here the authors report the rational design and construction of a catalytically active miniature sMMO which enables high-yield production of methanol in E. coli.

    • Yeonhwa Yu
    • , Yongfan Shi
    •  & Jeewon Lee
  • Article
    | Open Access

    The use of orthogonal genetic code can help to prevent the escape of hazardous genes through horizontal gene transfer. Here, the authors develop a cell-free translation system with the Ser/Leu-swapped genetic code using a hybrid tRNA set and show its application in enhancing the production of superfolder GFP.

    • Tomoshige Fujino
    • , Ryogo Sonoda
    •  & Hiroshi Murakami
  • Article
    | Open Access

    Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.

    • Nicholas C. Tang
    • , Jonathan C. Su
    •  & Ashutosh Chilkoti
  • Article
    | Open Access

    Bergenin is a rare C-glycoside of 4-O-methyl gallic acid with multiple pharmacological properties. Here, the authors report the elucidation of the biosynthetic pathway of bergenin in Ardisia japonica and its bioproduction by engineered E. coli.

    • Ruiqi Yan
    • , Binghan Xie
    •  & Lin Yang
  • Perspective
    | Open Access

    Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. In this Perspective, the authors propose an integrated solution combining growth-coupled selection with machine learning and automated workflows to accelerate development pipelines.

    • Enrico Orsi
    • , Lennart Schada von Borzyskowski
    •  & Steffen N. Lindner
  • 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

    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

    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

    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

    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

    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

    The ability to edit large stretches of mRNA transcripts remains a significant challenge. Here, the authors demonstrate that CRISPR-Cas13 systems can be repurposed to assist trans-splicing of exogenous RNA fragments into an endogenous pre-mRNA transcript, a method termed CRISPR Assisted mRNA Fragment Trans-splicing (CRAFT).

    • David N. Fiflis
    • , Nicolas A. Rey
    •  & Aravind Asokan
  • 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

    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

    Conditional degradation of proteins is instrumental to advance our knowledge of cell biology but has been lacking for organelles like mitochondria. Here, the authors develop a proteolysis system based on the mycoplasma Lon protease that functions selectively within mitochondria in yeast and human cells.

    • Swastika Sanyal
    • , Anna Kouznetsova
    •  & Camilla Björkegren
  • 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

    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

    The rapid identification of drug-resistant bacteria is vital for effective treatment and to avoid antibiotic misuse. Here authors report a paper-based sensor which utilises chromogenic carbapenem and cephalosporin substrates for the identification and discrimination of β-lactamase subtypes.

    • Wenshuai Li
    • , Jingqi Li
    •  & Dingbin Liu
  • Article
    | Open Access

    Cas13 systems suffer from a lack of spatiotemporal control. Here the authors report paCas13, a light-inducible Cas13 system created by fusing Magnet with fragment pairs; they also report padCas13, a light-inducible base-editing system by fusing ADAR2 to catalytically inactive paCas13 fragments.

    • Jeonghye Yu
    • , Jongpil Shin
    •  & Won Do Heo
  • 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

    In contrast to their clinical success as inhibitors and targeting agents, antibodies have generally been ineffective as receptor agonists. Here, Romei et al. leverage a natural homotypic interface to tune antibody geometry, enabling optimization of agonist activity for multiple therapeutic targets.

    • Matthew G. Romei
    • , Brandon Leonard
    •  & Greg A. Lazar
  • 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

    Targeting gluten antigens presents a plausible therapy option for celiac disease. Here the authors generate and characterize a broadly neutralizing antibody recognizing more than 25 gluten peptide:HLA-DQ2.5 complexes, with structural analyses implicating its mode of interaction, and with mouse in vivo studies supporting its therapeutic feasibility.

    • Yuu Okura
    • , Yuri Ikawa-Teranishi
    •  & Tomoyuki Igawa
  • 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