Abstract：
:The engineering of bacteria to controllably deliver therapeutics is an attractive application for synthetic biology. While most synthetic gene networks have been explored within microbes, there is a need for further characterization of in vivo circuit behavior in the context of applications where the host microbes are actively being investigated for efficacy and safety, such as tumor drug delivery. One major hurdle is that culture-based selective pressures are absent in vivo, leading to strain-dependent instability of plasmid-based networks over time. Here, we experimentally characterize the dynamics of in vivo plasmid instability using attenuated strains of S. typhimurium and real-time monitoring of luminescent reporters. Computational modeling described the effects of growth rate and dosage on live-imaging signals generated by internal bacterial populations. This understanding will allow us to harness the transient nature of plasmid-based networks to create tunable temporal release profiles that reduce dosage requirements and increase the safety of bacterial therapies.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Danino T,Lo J,Prindle A,Hasty J,Bhatia SNdoi
10.1021/sb3000639subject
Has Abstractpub_date
2012-10-19 00:00:00pages
465-470issue
10issn
2161-5063journal_volume
1pub_type
杂志文章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
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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
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journal_title：ACS synthetic biology
pub_type： 杂志文章
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journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:A gene-directed chemical communication pathway between synthetic protocell signaling transmitters (lipid vesicles) and receivers (proteinosomes) was designed, built and tested using a bottom-up modular approach comprising small molecule transcriptional control, cell-free gene expression, porin-directed efflux, substra...
journal_title：ACS synthetic biology
pub_type： 信件
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abstract：:A defining goal of synthetic biology is to develop biomaterials with superior performance and versatility. Here we introduce a purely genetically encoded and self-assembling biopolymer based on the SpyTag-SpyCatcher chemistry. We show the application of this polymer for highly efficient uranyl binding and extraction f...
journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:Cellobiose phosphorylase (CBP) cleaves cellobiose-abundant in plant biomass-to glucose and glucose 1-phosphate. However, the pentose sugar xylose, also abundant in plant biomass, acts as a mixed-inhibitor and a substrate for the reverse reaction, limiting the industrial potential of CBP. Preventing xylose, which lacks...
journal_title：ACS synthetic biology
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journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:We developed a hybrid synthetic circuit that co-opts the genetic regulation of the native bacterial quorum sensing autoinducer-2 and imposes an extra external controller for maintaining tightly controlled gene expression. This dual-input genetic controller was mathematically modeled and, by design, can be operated in ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:Strain engineering for synthetic biology and metabolic engineering applications often requires the expression of foreign proteins that can reduce cellular fitness. In order to quantify and visualize the evolutionary stability dynamics in engineered populations of Escherichia coli , we constructed randomized CMY (cyan-...
journal_title：ACS synthetic biology
pub_type： 杂志文章
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更新日期：2013-09-20 00:00:00
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journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:Fucosyl-oligosaccharides (FOSs) play physiologically important roles as prebiotics, neuronal growth factors, and inhibitors of enteropathogens. However, challenges in designed synthesis and mass production of FOSs hamper their industrial applications. Here, we report flexible biosynthetic routes to produce various FOS...
journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:To elucidate the function of mevalonate-5-pyrophosphate decarboxylase (MVD) and farnesyl pyrophosphate synthase (FPS) in triterpene biosynthesis, the genes governing the expression of these enzymes were transformed into Panax ginseng hairy roots. All the transgenic lines showed higher expression levels of PgMVD and Pg...
journal_title：ACS synthetic biology
pub_type： 杂志文章
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更新日期：2014-10-17 00:00:00
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journal_title：ACS synthetic biology
pub_type： 杂志文章
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abstract：:The extracellular expression of recombinant proteins using laboratory strains of Escherichia coli is now routinely achieved using naturally secreted substrates, such as YebF or the osmotically inducible protein Y (OsmY), as carrier molecules. However, secretion efficiency through these pathways needs to be improved fo...
journal_title：ACS synthetic biology
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abstract：:Dissimilatory metal-reducing bacteria, particularly those from the genus Shewanella, are of importance for bioremediation of metal contaminated sites and sustainable energy production. However, studies on this species have suffered from a lack of effective genetic tools for precise and high throughput genome manipulat...
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pub_type： 杂志文章
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更新日期：2013-11-15 00:00:00
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journal_title：ACS synthetic biology
pub_type： 杂志文章
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更新日期：2016-11-18 00:00:00
abstract：:In response to emergent antibiotic resistance, new strategies are needed to enhance the effectiveness of existing antibiotics. Here, we describe a phagemid-delivered, RNA-mediated system capable of directly knocking down antibiotic resistance phenotypes. Small regulatory RNAs (sRNAs) were designed to specifically inhi...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500033d
更新日期：2014-12-19 00:00:00
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journal_title：ACS synthetic biology
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