Synthetic biology articles within Nature Communications

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  • Perspective
    | Open Access

    Synthetic biology uses cells as its computing substrate, often based on the genetic circuit concept. In this Perspective, the authors argue that existing synthetic biology approaches based on classical models of computation limit the potential of biocomputing, and propose that living organisms have under-exploited capabilities.

    • Lewis Grozinger
    • , Martyn Amos
    •  & Angel Goñi-Moreno

  • Article
    | Open Access

    Existing efforts have been focused on one of the elements in the automation of the design, build, test, and learn (DBTL) cycle for biosystems design. Here, the authors integrate a robotic system with machine learning algorithms to fully automate the DBTL cycle and apply it in optimizing the lycopene biosynthetic pathway.

    • Mohammad HamediRad
    • , Ran Chao
    •  & Huimin Zhao

  • Article
    | Open Access

    Flexizymes have been used to expand the scope of chemical substrates for ribosome-directed polymerization in vitro. Here the authors deduce design rules of Flexizyme-mediated tRNA acylation that more effectively predict the incorporation of new monomers into peptides.

    • Joongoo Lee
    • , Kenneth E. Schwieter
    •  & Michael C. Jewett

  • Article
    | Open Access

    Microbial production of aromatic amino acid (AAA)-derived chemicals remains an outstanding metabolic engineering challenge. Here, the authors engineer baker’s yeast for high levels p-coumaric acid production by rewiring the central carbon metabolism and channeling more flux to the AAA biosynthetic pathway.

    • Quanli Liu
    • , Tao Yu
    •  & Yun Chen

  • Article
    | Open Access

    It is difficult to improve the efficacy of oncolytic virotherapy due to immune system responses and limited understanding of population dynamics. Here the authors use synthetic biology gene circuits to control adenoviral replication and release of immunomodulators in hepatocellular carcinoma cells.

    • Huiya Huang
    • , Yiqi Liu
    •  & Zhen Xie

  • Article
    | Open Access

    Cellular systems have numerous mechanisms to control gene expression. Here the authors build a Tet-On system with conditional destablising elements to regulate gene expression and protein stability, allowing fine modulation of mESC signalling pathways.

    • Elisa Pedone
    • , Lorena Postiglione
    •  & Lucia Marucci

  • Article
    | Open Access

    Protein phosphatases play an essential role in signal transduction, but are understudied due to the difficulties in detecting phosphate removal and the lack of good inhibitors. Here the authors develop a light-activated protein phosphatase using photocaged, unnatural amino acids and use it to study ERK nuclear translocation.

    • Taylor M. Courtney
    •  & Alexander Deiters

  • Article
    | Open Access

    Synthetic RNA-based devices can dynamically control a wide range of processes. Here the authors develop a quantitative and high-throughput mammalian cell-based RNA-seq assay to efficiently engineer ribozyme switches.

    • Joy S. Xiang
    • , Matias Kaplan
    •  & Christina D. Smolke

  • Article
    | Open Access

    Epistasis underlies the complexity of genotype-phenotype maps. Here, the authors analyze 8,192 mutants that link two phenotypically distinct variants of the Entacmaea quadricolor fluorescent protein, and show the existence, but also the sparsity, of high-order epistatic interactions.

    • Frank J. Poelwijk
    • , Michael Socolich
    •  & Rama Ranganathan

  • Article
    | Open Access

    Crosstalk between genetic circuits is a major challenge for engineering sophisticated networks. Here the authors design networks that compensate for crosstalk by integrating, not insulating, pathways.

    • Isaak E. Müller
    • , Jacob R. Rubens
    •  & Timothy K. Lu

  • Article
    | Open Access

    Ribo-T is a tethered ribosome complex capable of orthogonal ribosome-mRNA functionality, but has low activity. Here the authors evolve new tether designs that support faster growth and increased protein expression.

    • Erik D. Carlson
    • , Anne E. d’Aquino
    •  & Michael C. Jewett

  • Article
    | Open Access

    So far, synthetic genetic circuits have relied on digital logic for information processing. Here the authors present metabolic perceptrons that use analog weighted adders to vary the contributions of multiple inputs, resulting in different classification functions.

    • Amir Pandi
    • , Mathilde Koch
    •  & Jean-Loup Faulon

  • Article
    | Open Access

    Titers of monoterpenoids production in yeast are low due to the fact that the geranyl diphosphate (GPP)-based pathway can redirect metabolic fluxes to growth. Here, the authors build an orthogonal pathway by selecting the cis isomer of GPP as an alternative precursor and achieve high titer monoterpene production.

    • Codruta Ignea
    • , Morten H. Raadam
    •  & Sotirios C. Kampranis

  • Article
    | Open Access

    Current flux rewiring technologies in metabolic engineering are mainly transcriptional regulation. Here, the authors build two sets of controllable protein units using engineered viral proteases and proteolytic signals, and utilize for increasing titers of shikimate and D-xylonate in E. coli.

    • Cong Gao
    • , Jianshen Hou
    •  & Liming Liu

  • Article
    | Open Access

    Construction of plasmids from multiple fragments often uses customised parts and leaves scars where fragments are joined. Here the authors develop a method for barcoding fragments and constructing plasmids in a scarless manner from a collection of standard parts.

    • Xiaoqiang Ma
    • , Hong Liang
    •  & Kang Zhou

  • Article
    | Open Access

    Bacillus subtilis has complex spatial and temporal gene expression patterns but currently lacks optogenetic tools to explore these processes. Here the authors import and debug a cyanobacterial green light sensor pathway and show that it enables precise optical control of gene expression.

    • Sebastian M. Castillo-Hair
    • , Elliot A. Baerman
    •  & Jeffrey J. Tabor

  • Article
    | Open Access

    The role of gene expression noise in the evolution of drug resistance in mammalian cells is unclear. Here, by uncoupling noise from mean expression of a drug resistance gene in CHO cells the authors show that noisy expression aids adaptation to high drug levels, but delays it at low drug levels.

    • Kevin S. Farquhar
    • , Daniel A. Charlebois
    •  & Gábor Balázsi

  • Article
    | Open Access

    Metabolic engineering requires the balancing of gene expression to obtain optimal output. Here the authors present COMPASS – COMbinatorial Pathway ASSembly – which uses plant-derived artificial transcription factors and cloning of thousands of DNA constructs in parallel to rapidly optimise pathways.

    • Gita Naseri
    • , Jessica Behrend
    •  & Bernd Mueller-Roeber

  • Article
    | Open Access

    Adoption of DNA as a data storage medium could be accelerated with specialized synthesis processes and codecs. The authors describe TdT-mediated DNA synthesis in which data is stored in transitions between non-identical nucleotides and the use of synchronization markers to provide error tolerance.

    • Henry H. Lee
    • , Reza Kalhor
    •  & George M. Church

  • Comment
    | Open Access

    Biofoundries provide an integrated infrastructure to enable the rapid design, construction, and testing of genetically reprogrammed organisms for biotechnology applications and research. Many biofoundries are being built and a Global Biofoundry Alliance has recently been established to coordinate activities worldwide.

    • Nathan Hillson
    • , Mark Caddick
    •  & Paul S. Freemont

  • Article
    | Open Access

    One method of controlling protein degradation is through the use of degrons. Here the authors present a toolbox of characterised degrons as a library to fine-tune biological gene-expression systems. Its application is demonstrated by a set of tunable synthetic pulse generators in mammalian cells.

    • Hélène Chassin
    • , Marius Müller
    •  & Martin Fussenegger

  • Article
    | Open Access

    Bioproduction of tetrahydropapaveroline (THP) is limited by the specificity of monoamine oxidase (MAO). Here, the authors identify an insect 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) that can bypass MAO for direct aldehyde production and demonstrate bifunctional switching of DHPAAS for efficient THP production.

    • Christopher J. Vavricka
    • , Takanobu Yoshida
    •  & Akihiko Kondo

  • Article
    | Open Access

    The understanding of liquid-liquid phase separation is crucial to cell biology and benefits from cell-mimicking in vitro assays. Here, the authors develop a microfluidic platform to study coacervate formation inside liposomes and show the potential of these hybrid systems to create synthetic cells.

    • Siddharth Deshpande
    • , Frank Brandenburg
    •  & Cees Dekker

  • Article
    | Open Access

    Gene-drives use CRISPR-Cas9 to be transmitted in a super-Mendelian fashion. Here the authors develop an allelic-drive for selective inheritance of a desired allele.

    • Annabel Guichard
    • , Tisha Haque
    •  & Ethan Bier

  • Article
    | Open Access

    The microbial synthesis of carbon-containing compounds from single carbon precursors is desirable, yet designed pathways to achieve this goal overlap with host metabolism. Here the authors design a de novo metabolic pathway to assimilate formaldehyde into acetyl-CoA that does not overlap with known metabolic networks.

    • Xiaoyun Lu
    • , Yuwan Liu
    •  & Huifeng Jiang

  • Article
    | Open Access

    Artificial cells need to be supplied with ATP as they lack internal systems of energy generation. Here the authors reconstruct ATP synthase and bacteriorhodopsins for light-driven ATP generation, powering transcription and translation.

    • Samuel Berhanu
    • , Takuya Ueda
    •  & Yutetsu Kuruma

  • Article
    | Open Access

    The tethered ribosome system Ribo-T supports cell proliferation though at a reduced rate. Here the authors show this is due to slower ribosome assembly instead of reduced functionality.

    • Nikolay A. Aleksashin
    • , Margus Leppik
    •  & Alexander S. Mankin

  • Article
    | Open Access

    Genome-reduced bacteria often show impaired growth under laboratory conditions. Here the authors use adaptive laboratory evolution to optimise growth performance and show transcriptome and translatome-wide remodeling of the organism.

    • Donghui Choe
    • , Jun Hyoung Lee
    •  & Byung-Kwan Cho

  • Article
    | Open Access

    Analogue regulation of gene expression is important for normal function in mammals but existing genetic technologies are designed to achieve ON/OFF control. Here the authors develop synthetic microRNA silencing-mediated fine-tuners (miSFITs) to precisely control target gene expression levels.

    • Yale S. Michaels
    • , Mike B. Barnkob
    •  & Tudor A. Fulga

  • Article
    | Open Access

    The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

    • Dacheng Ma
    • , Zhimeng Xu
    •  & Zhen Xie

  • Article
    | Open Access

    Genetic logic devices allow the host cell to incorporate multiple inputs to determine output behaviour. Here the authors provide a framework for engineering reliable recombinase-based devices and demonstrate 4-input logic in a multicellular system.

    • Sarah Guiziou
    • , Pauline Mayonove
    •  & Jerome Bonnet

  • Article
    | Open Access

    Biological complexity has impeded our ability to predict the dynamics of mutualistic interactions. Here, the authors deduce a general rule to predict outcomes of mutualistic systems and introduce an approach that permits making predictions even in the absence of knowledge of mechanistic details.

    • Feilun Wu
    • , Allison J. Lopatkin
    •  & Lingchong You

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