Molecular engineering articles within Nature Communications

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  • Article
    | Open Access

    Non-ribosomal peptide synthases are multimodular enzymes comprised of adenylation (A), condensation (C) and thiolation domains. Here, the authors show that non-ribosomal peptides can be generated solely by A domain substitutions, providing evidence that the postulated substrate specifying role of C-domains may be rare in nature.

    • Mark J. Calcott
    • , Jeremy G. Owen
    •  & David F. Ackerley

  • Article
    | Open Access

    Natural speciation can be driven by pre-zygotic and post-zygotic barriers. Here the authors use a dominant lethal transgene coupled to a recessive resistance allele to engineer species-like barriers in Drosophila.

    • Maciej Maselko
    • , Nathan Feltman
    •  & Michael J. Smanski

  • Article
    | Open Access

    Self-propagating drives allow for non-Mendelian inheritance. Here the authors use CRISPR to build a chromosome drive, showing elimination of entire chromosomes, endoreduplication of desired chromosomes and enabling preferential transmissions of complex genetic traits on a chromosomal scale in yeast.

    • Hui Xu
    • , Mingzhe Han
    •  & Ying-Jin Yuan

  • Article
    | Open Access

    Backbone extended monomers are poorly compatible with the natural ribosomes, impeding their polymerization into polypeptides. Here the authors design non-canonical amino acid analogs with cyclic structures or extended carbon chains and used an engineered ribosome to improve tRNA-charging and incorporation into peptides.

    • Joongoo Lee
    • , Kevin J. Schwarz
    •  & Michael C. Jewett

  • Article
    | Open Access

    A cell free or synthetic biochemistry approach offers a way to circumvent the many constraints of living cells. Here, the authors demonstrate, via enzyme and process enhancements, the production of isobutanol with the metrics exceeding highly developed ethanol fermentation.

    • Saken Sherkhanov
    • , Tyler P. Korman
    •  & James U. Bowie

  • Article
    | Open Access

    Regulatory networks respond to environmental and genetic perturbations by reprogramming metabolism. Here the authors screen a library of 82 regulators with 110,120 mutations to map the regulatory network of 4000 genes.

    • Rongming Liu
    • , Liya Liang
    •  & Ryan T. Gill

  • Article
    | Open Access

    The ability to reversibly control monobody binding affinity would find use in biotechnology and research applications. Here the authors fuse the light-sensitive AsLOV2 domain to a monobody against the Abl SH2 domain to obtain a light dependent monobody and apply it in vitro and in mammalian cells.

    • César Carrasco-López
    • , Evan M. Zhao
    •  & José L. Avalos

  • Article
    | Open Access

    Cas9 fusions partners are often limited to natural polypeptide chains at the Cas9 termni. Here the authors present a platform for site-specific and multiple-site conjugation to both termini and internal sites of Cas9, and they apply this platform to efficiently engineer insulin-producing β cells.

    • Donghyun Lim
    • , Vedagopuram Sreekanth
    •  & Amit Choudhary

  • Article
    | Open Access

    The ability to regulate nanobody affinity with light would expand the applications toolbox for these reagents. Here the authors insert an optimised photoswitchable AsLOV2 domain into multiple nanobodies and demonstrate photoswitchable binding to fluorescent proteins and endogenous proteins in cells.

    • Agnieszka A. Gil
    • , César Carrasco-López
    •  & Jared E. Toettcher

  • Article
    | Open Access

    Genetically encoded voltage indicators (GEVIs) allow visualisation of fast action potentials in neurons but most are bright at rest and dimmer during an action potential. Here, the authors engineer electrochromic FRET GEVIs with fast, bright and positive-going fluorescence signals for in vivo imaging.

    • Ahmed S. Abdelfattah
    • , Rosario Valenti
    •  & Eric R. Schreiter

  • Article
    | Open Access

    DNA is an attractive digital data storing medium due to high information density and longevity. Here the authors use millions of sequences to investigate inherent biases in DNA synthesis and PCR amplification.

    • Yuan-Jyue Chen
    • , Christopher N. Takahashi
    •  & Karin Strauss

  • Article
    | Open Access

    Insect population control using conditional lethal systems could break down due to spontaneous mutations that render the system ineffective. Here the authors analyse the structure and frequency of such mutations in Drosophila and suggest the use of dual lethality systems to mitigate their survival.

    • Yang Zhao
    • , Marc F. Schetelig
    •  & Alfred M. Handler

  • Article
    | Open Access

    Control over splicing could be used for both therapeutic and engineering applications. Here the authors create artificial splicing factors using RNA-targeting CRISPR systems under small molecule control.

    • Menghan Du
    • , Nathaniel Jillette
    •  & Albert Wu Cheng

  • Article
    | Open Access

    The physical architectures of information storage dictate how data is encoded, organised and accessed. Here the authors use DNA with a single-strand overhang as a physical address to access specific data and do in-storage file operations in a scalable and reusuable manner.

    • Kevin N. Lin
    • , Kevin Volkel
    •  & Albert J. Keung

  • Article
    | Open Access

    Previous design strategies for pH sensitive aptamers were not readily tunable across pH ranges. Here the authors present a general method to convert aptamers into pH-responsive switches using two orthogonal motifs.

    • Ian A. P. Thompson
    • , Liwei Zheng
    •  & H. Tom Soh

  • Article
    | Open Access

    Some human amyloid proteins have been shown to interact with viral proteins, suggesting that they may have potential as therapeutic agents. Here the authors design synthetic amyloids specific for influenza A and Zika virus proteins, respectively, and show that they can inhibit viral replication.

    • Emiel Michiels
    • , Kenny Roose
    •  & Joost Schymkowitz

  • Article
    | Open Access

    While organisms like squid can adaptively modulate the optical properties of their tissues, human cells lack analogous abilities. Here the authors engineer human cells to produce protein architectures with tunable light scattering functionalities.

    • Atrouli Chatterjee
    • , Juana Alejandra Cerna Sanchez
    •  & Alon A. Gorodetsky

  • Article
    | Open Access

    Protospacer adjacent motif (PAM) requirements limit the target range of CRISPR endonucleases. Here, the authors graft the 5\(^{\prime}\)-NAAN-3\(^{\prime}\) PAM-interacting domain of SmacCas9 onto SpyCas9 to create adenine dinucleotide targeting chimeras.

    • Pranam Chatterjee
    • , Jooyoung Lee
    •  & Noah Jakimo

  • Review Article
    | Open Access

    Our efforts to build complex synthetic biology circuits are impeded by limited knowledge of optimal combinations. In this review, the authors consider current combinatorial methods and look to emerging technologies.

    • Gita Naseri
    •  & Mattheos A. G. Koffas

  • Article
    | Open Access

    The spatial organisation of microbial communities is caused by the interplay of biotic and abiotic factors. Here the authors design a microfluidic platform to quantify the spatiotemporal parameters influencing diffusion-mediated interactions, and use this device to investigate information transmission and metabolic cross-feeding in synthetic microbial consortia.

    • Sonali Gupta
    • , Tyler D. Ross
    •  & Ophelia S. Venturelli

  • Article
    | Open Access

    Noninvasive detection of molecular targets in living subjects could provide valuable insights into healthy function and disease. Here, the authors develop vasoactive imaging probes which allow wide-field in vivo mapping of nanomolar-level molecular species in rat brain.

    • Robert Ohlendorf
    • , Agata Wiśniowska
    •  & Alan Jasanoff

  • Article
    | Open Access

    Lactazole A is a thiopeptide from Streptomyces lactacystinaeus, encoded by a compact 9.8 kb biosynthetic gene cluster. Here, the authors show a platform for in vitro biosynthesis of lactazole A via a combination of a flexible in vitro translation system with recombinantly produced lactazole biosynthetic enzymes.

    • Alexander A. Vinogradov
    • , Morito Shimomura
    •  & Hiroyasu Onaka

  • Article
    | Open Access

    Cellular markers of endothelial cell proliferation help identify the vasculature of tumours in homeostasis. Here, the authors report Apelin-based synthetic Notch (synNotch) receptors that can target Apj expressed on endothelium and stimulate the synNotch pathways upon Apj binding, and suggest this as a strategy to treat solid tumours.

    • Zhifu Wang
    • , Fan Wang
    •  & Jianhong Zhu

  • Article
    | Open Access

    A small set of promoters is used for most genetic construct design in S. cerevisiae. Here, the authors develop a predictive model of promoter activity trained on a data set of over one million sequences and use it to design large sets of high-activity promoters.

    • Benjamin J. Kotopka
    •  & Christina D. Smolke

  • Article
    | Open Access

    Many industrial organisms are the result of recent or ancient allopolypoidy events. Here the authors iteratively combine the genomes of six yeast species to generate a viable hybrid.

    • David Peris
    • , William G. Alexander
    •  & Chris Todd Hittinger

  • Article
    | Open Access

    Malate dehydrogenase (MDH) is one of the key enzymes for succinic acid (SA) bioproduction. Here, the authors report biochemical and structural analyses of various MDHs to reveal amino acids influencing the specific activity and susceptibility to substrate inhibition, and achieve industrial-level SA production.

    • Jung Ho Ahn
    • , Hogyun Seo
    •  & Sang Yup Lee

  • Article
    | Open Access

    Ribosome engineering is an emerging powerful approach for synthetic protein synthesis. Here the authors invert the Ribo-T system, using the engineered ribosome to translate the proteome while the native ribosome translates specific mRNA.

    • Nikolay A. Aleksashin
    • , Teresa Szal
    •  & Alexander S. Mankin

  • Article
    | Open Access

    Current synthetic DNA-based data storage systems have high recording costs, read-write latency and error-rates that make them uncompetitive compared to traditional digital storage. The authors use nicks in native DNA to encode data in parallel and create access sites for in-memory computations.

    • S. Kasra Tabatabaei
    • , Boya Wang
    •  & Olgica Milenkovic

  • Article
    | Open Access

    The spectra of light used by photosynthetic organisms are determined by their pigmentation colour palettes. Here Liu et al. show that a genetically-encoded chimera of light-harvesting proteins from plants and reaction centres from purple bacteria allows for polychromatic solar energy harvesting.

    • Juntai Liu
    • , Vincent M. Friebe
    •  & Michael R. Jones

  • Article
    | Open Access

    Genetic variation in natural populations could represent gene drive resistant alleles, preventing successful application for population management. Here the authors survey 1280 genomes from three mosquito species and concludes natural variation will not be detrimental to deploying gene drive technology.

    • Hanno Schmidt
    • , Travis C. Collier
    •  & Gregory C. Lanzaro

  • Article
    | Open Access

    Major Histocompatibility Complex (MHC) class I molecules present tightly binding peptides on the cell surface for recognition by cytotoxic T cells. Here, the authors present the crystal structures of a disulfide-stabilized human MHC class I molecule in the peptide-free state and bound with dipeptides, and find that peptide binding is accompanied by concerted conformational switches of the amino acid side chains in the binding pockets.

    • Raghavendra Anjanappa
    • , Maria Garcia-Alai
    •  & Rob Meijers

  • Article
    | Open Access

    Cell surface proteins mediate the interactions between cells and their extracellular environment. Here the authors design synthetic biomemetic receptor-like sensors that facilitate programmable interactions between bacteria and their target.

    • Naama Lahav-Mankovski
    • , Pragati Kishore Prasad
    •  & David Margulies

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