Abstract：
:Synthetic biology holds promise to engineer systems to treat diseases. One critical, yet underexplored, facet of designing such systems is the interplay between the system and the pathogen. Understanding this interplay may be critical to increasing efficacy and overcoming resistance against the system. Using the principles of synthetic biology, we engineer a strain of Escherichia coli to attract and intoxicate the nematode Caenorhabditis elegans. Our bacteria are engineered with a toxin module, which intoxicates the nematode upon ingestion, and an attraction module, which serves to attract and increase the feeding rate of the nematodes. When independently implemented, these modules successfully intoxicate and attract the worms, respectively. However, in combination, the efficacy of our bacteria is significantly reduced due to aversive associative learning in C. elegans. Guided by mathematical modeling, we dynamically regulate module induction to increase intoxication by circumventing learning. Our results detail the creation of a novel nematicidal bacterium that may have application against nematodes, unravel unique constraints on circuit dynamics that are governed by C. elegans physiology, and add to the growing list of design and implementation considerations associated with synthetic biology.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Bracho OR,Manchery C,Haskell EC,Blanar CA,Smith RPdoi
10.1021/acssynbio.5b00192subject
Has Abstractpub_date
2016-03-18 00:00:00pages
241-9issue
3issn
2161-5063journal_volume
5pub_type
杂志文章abstract：:The measurement of gene expression using fluorescence markers has been a cornerstone of synthetic biology for the past two decades. However, the use of arbitrary units has limited the usefulness of these data for many quantitative purposes. Calibration of fluorescence measurements from flow cytometry and plate reader ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00296
更新日期：2020-09-18 00:00:00
abstract：:Antimycins are a family of natural products generated from a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line. Although they possess an array of useful biological activities, their structural complexity makes chemical synthesis challenging, and their biosynthesis has thus far been ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb5003136
更新日期：2015-05-15 00:00:00
abstract：:Cell-free systems, as part of the synthetic biology field, have become a critical platform in biological studies. However, there is a lack of research into developing a switch for a dynamical control of the transcriptional and translational process. The optogenetic tool has been widely proven as an ideal control switc...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00211
更新日期：2020-08-21 00:00:00
abstract：:Combinatorial metabolic engineering has been widely established for the development of efficient microbial cell factories to produce the products of interest by precisely regulating the expression levels of multiple genes simultaneously. Here, we report a novel multifunctional CRISPR system that enables simultaneous g...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00218
更新日期：2020-09-18 00:00:00
abstract：:Optogenetic tools can provide direct and programmable control of gene expression. Light-inducible recombinases, in particular, offer a powerful method for achieving precise spatiotemporal control of DNA modification. However, to-date this technology has been largely limited to eukaryotic systems. Here, we develop opto...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00395
更新日期：2020-02-21 00:00:00
abstract：:Engineered bacteria promise to revolutionize diagnostics and therapeutics, yet many applications are precluded by the limited number of detectable signals. Here we present a general framework to engineer synthetic receptors enabling bacterial cells to respond to novel ligands. These receptors are activated via ligand-...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00266
更新日期：2018-01-19 00:00:00
abstract：:Recent advances in the design and construction of synthetic multicelled systems in E. coli and S. cerevisiae suggest that it may be possible to implement sophisticated distributed algorithms with these relatively simple organisms. However, existing design frameworks for synthetic biology do not account for the unique ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb300034m
更新日期：2012-08-17 00:00:00
abstract：:Metabolic engineering of Escherichia coli was performed to construct a 100% rationally engineered strain capable of overproducing L-isoleucine, an important branched-chain amino acid. The thrABC (encoding L-threonine biosynthetic enzymes), ilvA (encoding feedback-resistant threonine dehydratase), ilvIH (encoding feedb...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb300071a
更新日期：2012-11-16 00:00:00
abstract：:As fast terminators of G-protein coupled receptor (GPCR) signaling, regulators of G-protein signaling (RGS) serve critical roles in fine-tuning second messenger levels and, consequently, cellular responses to external stimuli. Here, we report the creation of an optogenetic RGS2 (opto-RGS2) that suppresses agonist-evok...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00065
更新日期：2018-06-15 00:00:00
abstract：:Transform-MinER (Transforming Molecules in Enzyme Reactions) is a web application facilitating the exploration of chemical biosynthetic space, guiding the user toward promising start points for enzyme design projects or directed evolution experiments. Two types of search are possible: Molecule Search allows a user to ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00105
更新日期：2019-11-15 00:00:00
abstract：:Many Gram-negative pathogens encode type 3 secretion systems, sophisticated nanomachines that deliver proteins directly into the cytoplasm of mammalian cells. These systems present attractive opportunities for therapeutic protein delivery applications; however, their utility has been limited by their inherent pathogen...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00002
更新日期：2015-05-15 00:00:00
abstract：:Mycoplasma hominis is a minimal human pathogen that is responsible for genital and neonatal infections. Despite many attempts, there is no efficient genetic tool to manipulate this bacterium, limiting most investigations of its pathogenicity and its uncommon energy metabolism that relies on arginine. The recent clonin...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00379
更新日期：2017-05-19 00:00:00
abstract：:Bacteria of the order Actinomycetales are one of the most important sources of pharmacologically active and industrially relevant secondary metabolites. Unfortunately, many of them are still recalcitrant to genetic manipulation, which is a bottleneck for systematic metabolic engineering. To facilitate the genetic mani...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00038
更新日期：2015-09-18 00:00:00
abstract：:While inducing agents are often used to redirect resources from growth and proliferation toward product outputs, they can be prohibitively expensive on the industrial scale. Previously, we developed an autonomously guided protein production system based on the rewiring of E. coli's native quorum sensing (QS) signal tr...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00261
更新日期：2016-09-16 00:00:00
abstract：:Directed evolution requires the creation of genetic diversity and subsequent screening or selection for improved variants. For DNA mutagenesis, conventional site-directed methods implicitly utilize the Boolean AND operator (creating all mutations simultaneously), producing a combinatorial explosion in the number of ge...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00063
更新日期：2019-06-21 00:00:00
abstract：:While predictable design of a genetic circuit's output is a major goal of synthetic biology, it remains a significant challenge because DNA binding sites in the cell affect the concentration of available transcription factors (TF). To mitigate this problem, we propose to use a TF that results from the (reversible) pho...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb5002533
更新日期：2015-05-15 00:00:00
abstract：:Staphylococci are prevalent skin-dwelling bacteria that are also leading causes of antibiotic-resistant infections. Viruses that infect and lyse these organisms (virulent staphylococcal phages) can be used as alternatives to conventional antibiotics and represent promising tools to eliminate or manipulate specific spe...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00240
更新日期：2017-12-15 00:00:00
abstract：:Lignans are plant secondary metabolites with a wide range of reported health-promoting bioactivities. Traditional routes toward these natural products involve, among others, the extraction from plant sources and chemical synthesis. However, the availability of the sources and the complex chemical structures of lignans...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00354
更新日期：2020-11-20 00:00:00
abstract：:Sporulated cells have potential as time-delayed expression chassis of proteins for applications such as "on-demand" biologics production, whole cell biosensors, or oral vaccines. However, the desired attributes of high expression rates and low product variances are difficult to maintain from germinated spores. In this...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00163
更新日期：2019-10-18 00:00:00
abstract：:Actinomycetes are important organisms for the biosynthesis of valuable natural products. However, only a limited number of well-characterized native constitutive promoters from actinomycetes are available for the construction and engineering of large biochemical pathways. Here, we report the discovery and characteriza...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00016
更新日期：2015-09-18 00:00:00
abstract：:Simple computation can be performed using the interactions between single-stranded molecules of DNA. These interactions are typically toehold-mediated strand displacement reactions in a well-mixed solution. We demonstrate that a DNA circuit with tethered reactants is a distributed system and show how it can be describ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00275
更新日期：2016-08-19 00:00:00
abstract：:Strategies to optimize a metabolic pathway often involve building a large collection of strains, each containing different versions of sequences that regulate the expression of pathway genes. Here, we develop reagents and methods to carry out this process at high efficiency in the yeast Saccharomyces cerevisiae. We id...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500363y
更新日期：2015-07-17 00:00:00
abstract：:Constructing efficient cellular factories often requires integration of heterologous pathways for synthesis of novel compounds and improved cellular productivity. Few genomic sites are routinely used, however, for efficient integration and expression of heterologous genes, especially in nonmodel hosts. Here, a data-gu...
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doi：10.1021/acssynbio.0c00299
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abstract：:Directed evolution experiments designed to improve the activity of a biocatalyst have increased in sophistication from the early days of completely random mutagenesis. Sequence-based and structure-based methods have been developed to identify "hotspot" positions that when randomized provide a higher frequency of benef...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00359
更新日期：2018-07-20 00:00:00
abstract：:Modern bioprocessing depends on superior cellular traits, many stemming from unknown genes and gene interactions. Tolerance to toxic chemicals is such an industrially important complex trait, which frequently limits the economic feasibility of producing commodity chemicals and biofuels. Chemical tolerance encompasses ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
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更新日期：2014-07-18 00:00:00
abstract：:The Design-Build-Test-Learn (DBTL) cycle, facilitated by exponentially improving capabilities in synthetic biology, is an increasingly adopted metabolic engineering framework that represents a more systematic and efficient approach to strain development than historical efforts in biofuels and biobased products. Here, ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00020
更新日期：2019-06-21 00:00:00
abstract：:Although recent advances in synthetic biology allow us to produce biological designs more efficiently than ever, our ability to predict the end result of these designs is still nascent. Predictive models require large amounts of high-quality data to be parametrized and tested, which are not generally available. Here, ...
journal_title：ACS synthetic biology
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doi：10.1021/acssynbio.7b00204
更新日期：2017-12-15 00:00:00
abstract：:To facilitate the construction of cell-free genetic devices, we evaluated the ability of 17 different fluorescent proteins to give easily detectable fluorescence signals in real-time from in vitro transcription-translation reactions with a minimal system consisting of T7 RNA polymerase and E. coli translation machiner...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb400003y
更新日期：2013-09-20 00:00:00
abstract：:Allosteric proteins, which can sense different signals, are interesting biological parts for synthetic biology. In particular, the design of an artificial allosteric enzyme to sense an unnatural signal is both challenging and highly desired, for example, for a precise and dynamical control of fluxes of growth-essentia...
journal_title：ACS synthetic biology
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doi：10.1021/sb400133g
更新日期：2015-02-20 00:00:00
abstract：:Prenylated aromatic compounds are important intermediates in the biosynthesis of bioactive molecules such as 3-chromanols from plants, ubiquinones from prokaryotes and meroterpenoids from sponges. Biosynthesis of prenylated aromatic compounds using prokaryotic microorganisms has attracted increasing attention in the f...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00070
更新日期：2018-09-21 00:00:00
