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| Open AccessA synthetic sex ratio distortion system for the control of the human malaria mosquito
Extreme reproductive sex ratios could result in the suppression or elimination of pest populations. Here, the authors design a synthetic sex distortion system in Anopheles gambiaethat gives rise to fertile mosquito strains that produce over 95% male offsprings and could therefore be used to suppress mosquito populations.
- Roberto Galizi
- , Lindsey A. Doyle
- & Andrea Crisanti
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Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling
Optogenetic tools allow fine spatial control of signalling pathways using light. Chang et al. present a strategy for constructing light-sensitive receptor tyrosine kinases and demonstrate that optogenetic stimulation of Trk receptors in neurons promotes neurite outgrowth.
- Ki-Young Chang
- , Doyeon Woo
- & Won Do Heo
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Genome engineering empowers the diatom Phaeodactylum tricornutum for biotechnology
Diatoms are photosynthetic microalgae with underutilized biotechnological potential. Here, the authors carry out targeted gene modifications of lipid metabolism genes in the diatom, Phaeodactylum tricornutum, resulting in a strain that exhibits a 45-fold increase in triacylglycerol accumulation.
- Fayza Daboussi
- , Sophie Leduc
- & Philippe Duchateau
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Design of synthetic yeast promoters via tuning of nucleosome architecture
Model-based part design is a key step in synthetic biology. Here, the authors report a method for tuning nucleosome architecture in order to strengthen native promoters and facilitate synthetic promoter design in yeast.
- Kathleen A. Curran
- , Nathan C. Crook
- & Hal S. Alper
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An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging
Infrared fluorescent proteins offer advantages for deep in vivo imaging thanks to the tissue-penetrating properties of infrared light. Here, Yu et al. design a monomeric infrared fluorescent protein that, when combined with expression of haeme oxygenase in cells, shows improved performance for in vivoimaging of neurons and brain tumours.
- Dan Yu
- , William Clay Gustafson
- & Xiaokun Shu
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| Open AccessThe seco-iridoid pathway from Catharanthus roseus
The (seco)iridoids and their monoterpenoid indole alkaloid (MIA) derivatives are plant-derived compounds with pharmaceutical applications. Here, the authors identify the last four missing steps of the (seco)iridoid pathway, which they reconstitute in an alternative plant host to produce the complex MIA, strictosidine.
- Karel Miettinen
- , Lemeng Dong
- & Danièle Werck-Reichhart
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| Open AccessA plant factory for moth pheromone production
Pheromones can be used as an environmentally friendly alternative to traditional pesticides. Here, the authors produce moth sex pheromones in Nicotiana benthamianaby transient expression and demonstrate that these pheromones are able to trap male moths as efficiently as their synthetic counterparts.
- Bao-Jian Ding
- , Per Hofvander
- & Christer Löfstedt
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Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae
Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in Saccharomyces cerevisiae, demonstrating the feasibility of producing commercially important alkaloids in microbial systems.
- Elena Fossati
- , Andrew Ekins
- & Vincent J. J. Martin
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A high-energy-density sugar biobattery based on a synthetic enzymatic pathway
Incomplete oxidation of fuels is a common problem in enzymatic fuel cells and it leads to low energy densities. Zhu et al. report the complete oxidation of sugar in an enzymatic fuel cell through a synthetic enzymatic pathway, which exhibits higher energy densities than lithium-ion batteries.
- Zhiguang Zhu
- , Tsz Kin Tam
- & Y. -H. Percival Zhang
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Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production
Bio-based production of oils and lipids could potentially provide a sustainable fuel alternative to petroleum. Here, the authors show that Yarrowia lipolytica’s metabolism can be rewired to saturate cells with upwards of 90% lipid content and significantly increase lipid production.
- John Blazeck
- , Andrew Hill
- & Hal S. Alper
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A fully genetically encoded protein architecture for optical control of peptide ligand concentration
The design of optogenetic tools to control ion channel function typically requires careful consideration of channel structure. Schmidt et al. present a modular strategy to engineer light sensitivity in several K+channels, which functions independently of exogenous chemical modulators.
- Daniel Schmidt
- , Paul W. Tillberg
- & Edward S. Boyden
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High efficiency cell-specific targeting of cytokine activity
Despite their clinical potential, cytokines can often be highly toxic in patients, due to their systemic activity. Here, the authors present a strategy to engineer immunocytokines with very high targeting efficacies using mutant cytokines linked to nanobodies that only become active when bound to a specific cell marker.
- Geneviève Garcin
- , Franciane Paul
- & Gilles Uzé
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Engineering protein thermostability using a generic activity-independent biophysical screen inside the cell
Methods to improve protein stability are important in the biopharmaceutical industry. Here, the authors describe a high-throughput screen to increase protein thermostability and identify thermostable variants from a broad range of proteins.
- Ignacio Asial
- , Yue Xiang Cheng
- & Tobias Cornvik
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Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster
Polycyclic tetramate macrolactams (PTMs) are natural products with important antifungal, antibiotic and antioxidant properties. Here, the authors apply a synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster from Streptomyces griseusand identify three putative PTMs.
- Yunzi Luo
- , Hua Huang
- & Huimin Zhao
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| Open AccessA closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice
Designer gene circuits allow the controlled expression of proteins in response to specific stimuli. Here, Rössger et al.use synthetic biology approaches to create a fatty-acid biosensor that controls the production of a satiety hormone and use it to control diet-induced obesity in mice.
- Katrin Rössger
- , Ghislaine Charpin-El-Hamri
- & Martin Fussenegger
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Tuning the range and stability of multiple phenotypic states with coupled positive–negative feedback loops
Interlocking positive and negative feedback loops are common in biological networks. By engineering separate external controls for both loops within the yeast galactose uptake system, Avendaño et al.show that this motif confers dual regulation of range and switching frequency between phenotypes.
- Maier S. Avendaño
- , Chad Leidy
- & Juan M. Pedraza
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Implementation of stable and complex biological systems through recombinase-assisted genome engineering
Genetic engineering of bacteria is an important tool in biotechnology and synthetic biology. Here, the authors describe a method for genomic integration of complex, multi-gene sequences into bacteria and use it to create a strain of E. colithat generates ethanol from brown macroalgae.
- Christine Nicole S. Santos
- , Drew D. Regitsky
- & Yasuo Yoshikuni
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Mutants of Cre recombinase with improved accuracy
Cre recombinase is widely used to precisely manipulate genes and chromosomes, but it often displays off-target activity. Here, the authors improve the accuracy of Cre-mediated recombination by introducing specific mutations in the enzyme’s dimerization surface.
- Nikolai Eroshenko
- & George M. Church
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Transferring a synthetic gene circuit from yeast to mammalian cells
Gene circuits created by synthetic biologists working in one system may not be functional when transferred to a different organism. Using computational modelling to identify factors underlying such differences, the authors successfully adapt a yeast ‘linearizer’ circuit so that it functions in mammalian cells.
- Dmitry Nevozhay
- , Tomasz Zal
- & Gábor Balázsi
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Synthetic RNA devices to expedite the evolution of metabolite-producing microbes
Genome-wide variation in the directed evolution of metabolite-overproducing microbes requires high-throughput screening platforms. Yang et al.show that synthetic RNA devices can sense target metabolites, enrich pathway optimisation, and expedite the evolution of metabolite-producing microbes.
- Jina Yang
- , Sang Woo Seo
- & Gyoo Yeol Jung
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Engineering RNA endonucleases with customized sequence specificities
Sequence-specific DNA endonucleases have found numerous applications in biology, but similar manipulations of RNA have been limited by the lack of suitable enzymes. These authors combine a cleavage domain with a designable binding domain and demonstrate the resulting RNA endonuclease's utilityin vitroand in cells.
- Rajarshi Choudhury
- , Yihsuan S. Tsai
- & Zefeng Wang
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Protein encapsulation within synthetic molecular hosts
Protein encapsulation in molecular cages has the potential to alter protein function and aid crystallization. Here, ubiquitin is encapsulated within a giant coordination cage; the protein is attached to a bidentate ligand, and the cage self-assembles upon addition of capping ligands and Pd(II) ions.
- Daishi Fujita
- , Kosuke Suzuki
- & Makoto Fujita
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| Open AccessStructure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor
Albumin transport proteins circulate in the blood and are protected from degradation by interaction with the neonatal Fc receptor. Andersenet al. investigate the albumin binding site of the neonatal Fc receptor and find pH sensitive ionic networks at the binding interface.
- Jan Terje Andersen
- , Bjørn Dalhus
- & Inger Sandlie
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| Open AccessSynthetic quorum-sensing circuit to control consortial biofilm formation and dispersal in a microfluidic device
Engineered biofilms have applications in biorefineries. Here, Honget al. engineer bacteria to produce a combination of dispersal proteins and quorum sensing factors, and show that one dispersing bacterium can eliminate a biofilm formed by a colonizing bacterium.
- Seok Hoon Hong
- , Manjunath Hegde
- & Thomas K. Wood
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| Open AccessEngineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology
Biological digital sensors require the fabrication of modular genetic logic gates. Using thePseudomonas syringae hrpsystem, Wang and colleagues generate AND, NOT and NAND gates, demonstrating the ability to engineer a modular system from biological elements.
- Baojun Wang
- , Richard I Kitney
- & Martin Buck
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| Open AccessIdentification and microbial production of a terpene-based advanced biofuel
Advanced biofuels with comparable properties to petroleum-based fuels could be microbially produced from lignocellulosic biomass. In this study,Escherichia coliis engineered to produce bisabolene, the immediate precursor of bisabolane, a biosynthetic alternative to D2 diesel.
- Pamela P. Peralta-Yahya
- , Mario Ouellet
- & Taek Soon Lee
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| Open AccessSynthetic human cell fate regulation by protein-driven RNA switches
The control of cell fate and apoptosis is a continuing challenge in synthetic biology. In this study, systems are developed in which an intracellularly expressed genome-encoded protein simultaneously achieves up- and downregulation of two distinct apoptosis pathways.
- Hirohide Saito
- , Yoshihiko Fujita
- & Tan Inoue