Abstract:
:A negating functionality is fundamental to information processing of logic circuits within cells and computers. Aiming to adapt unutilized electronic concepts to the interrogation of signaling circuits in cells, we first took a bottom-up strategy whereby we created protein-based devices that perform negating Boolean logic operations such as NOT, NOR, NAND, and N-IMPLY. These devices function in living cells within a minute by precisely commanding the localization of an activator molecule among three subcellular spaces. We networked these synthetic gates to an endogenous signaling circuit and devised a physiological output. In search of logic functions in signal transduction, we next took a top-down approach and computationally screened 108 signaling pathways to identify commonalities and differences between these biological pathways and electronic circuits. This combination of synthetic and systems approaches will guide us in developing foundations for deconstruction of intricate cell signaling, as well as construction of biomolecular computers.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Razavi S,Su S,Inoue Tdoi
10.1021/sb500222zsubject
Has Abstractpub_date
2014-09-19 00:00:00pages
676-85issue
9issn
2161-5063journal_volume
3pub_type
杂志文章abstract::RNA parts often serve as critical components in genetic engineering. Here we report a design of translational activators which is composed of an RNA endoribonuclease (Csy4) and two exchangeable RNA modules. Csy4, a member of Cas endoribonuclease, cleaves at a specific recognition site; this cleavage releases a cis-rep...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.5b00130
更新日期:2016-01-15 00:00:00
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
doi:10.1021/acssynbio.0c00179
更新日期:2020-10-16 00:00:00
abstract::As a product of a multistep enzymatic reaction, accumulation of poly(3-hydroxybutyrate) (PHB) in Escherichia coli (E. coli) can be achieved by overexpression of the PHB synthesis pathway from a native producer involving three genes phbC, phbA, and phbB. Pathway optimization by adjusting expression levels of the three ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00083
更新日期:2016-11-18 00:00:00
abstract::Increasing protein expression levels is a key step in the commercial production of enzymes. Predicting promoter activity and translation initiation efficiency based solely on consensus sequences have so far met with mixed results. Here, we addressed this challenge using a "brute-force" approach by designing and synthe...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00110
更新日期:2018-07-20 00:00:00
abstract::In this work, we develop methodologies for analyzing and cross comparing metabolic models. We investigate three important metabolic networks to discuss the complexity of biological organization of organisms, modeling, and system properties. In particular, we analyze these metabolic networks because of their biotechnol...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb300102k
更新日期:2013-05-17 00:00:00
abstract::Microbial electrosynthesis is an emerging technology with the potential to simultaneously store renewably generated energy, fix carbon dioxide, and produce high-value organic compounds. However, limited understanding of the route of electrons into the cell remains an obstacle to developing a robust microbial electrosy...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00498
更新日期:2019-07-19 00:00:00
abstract::Characterization of genetic control elements is essential for the predictable engineering of synthetic biology systems. The current standard for in vivo characterization of control elements is through the use of fluorescent reporter proteins such as green fluorescent protein (GFP). Gene expression, however, involves n...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb400089c
更新日期:2014-03-21 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::Most of the current methods for controlling the formation rate of a key protein or enzyme in cell factories rely on the manipulation of target genes within the pathway. In this article, we present a novel synthetic system for post-translational regulation of protein levels, FENIX, which provides both independent contr...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00345
更新日期:2018-11-16 00:00:00
abstract::Secondary structure formation of mRNA, caused by desynchronization of transcription and translation, is known to impact gene expression in vivo. Yet, inactivation of mRNA by secondary structures in cell-free protein expression is frequently overlooked. Transcription and translation rates are often not highly synchroni...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00010
更新日期:2016-12-16 00:00:00
abstract::The heteroduplex hybridization thermodynamics of DNA with either RNA or TNA are greatly affected by DNA pyrimidine content, where increased DNA pyrimidine content leads to significantly increased duplex stability. Little is known, however, about the effect that purine or pyrimidine content has on the hybridization kin...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00471
更新日期:2020-02-21 00:00:00
abstract::Type I modular polyketide synthases (PKSs) are polymerases that utilize acyl-CoAs as substrates. Each polyketide elongation reaction is catalyzed by a set of protein domains called a module. Each module usually contains an acyltransferase (AT) domain, which determines the specific acyl-CoA incorporated into each conde...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00176
更新日期:2017-01-20 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...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.0c00299
更新日期:2020-09-18 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::Feedback allows biological systems to control gene expression precisely and reliably, even in the presence of uncertainty, by sensing and processing environmental changes. Taking inspiration from natural architectures, synthetic biologists have engineered feedback loops to tune the dynamics and improve the robustness ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00040
更新日期:2018-05-18 00:00:00
abstract::Glycolate is an important α-hydroxy acid with a wide range of industrial applications. The current industrial production of glycolate mainly depends on chemical synthesis, but biochemical production from renewable resources using engineered microorganisms is increasingly viewed as an attractive alternative. Crude glyc...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.0c00404
更新日期:2020-09-18 00:00:00
abstract::In this work we report synthetic adhesins (SAs) enabling the rational design of the adhesion properties of E. coli. SAs have a modular structure comprising a stable β-domain for outer membrane anchoring and surface-exposed immunoglobulin domains with high affinity and specificity that can be selected from large repert...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb500252a
更新日期:2015-04-17 00:00:00
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
doi:10.1021/sb400194g
更新日期:2014-10-17 00:00:00
abstract::Living organisms employ endogenous negative feedback loops to maintain homeostasis despite environmental fluctuations. A pressing open challenge in Synthetic Biology is to design and implement synthetic circuits to control host cells' behavior, in order to regulate and maintain desired conditions. To cope with the hig...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00220
更新日期:2017-03-17 00:00:00
abstract::Cell-free protein synthesis (CFPS) is a widely used research tool in systems and synthetic biology. However, if CFPS is to become a mainstream technology for applications such as point of care manufacturing, we must understand the performance limits and costs of these systems. Toward this question, we used sequence sp...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.7b00465
更新日期:2018-08-17 00:00:00
abstract::Episodic gene expression, with periods of high expression separated by periods of no expression, is a pervasive biological phenomenon. This bursty pattern of expression draws from a finite reservoir of expression machinery in a highly time variant way, i.e., requiring no resources most of the time but drawing heavily ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00189
更新日期:2017-02-17 00:00:00
abstract::Heterochiral DNA strand-displacement reactions enable sequence-specific interfacing of oligonucleotide enantiomers, making it possible to interface native d-nucleic acids with molecular circuits built using nuclease-resistant l-DNA. To date, all heterochiral reactions have relied on peptide nucleic acid (PNA), which p...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00335
更新日期:2019-12-20 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
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
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00366
更新日期:2017-05-19 00:00:00
abstract::The Sc2.0 project is perhaps the largest synthetic biology project in the public domain, and ultimately aims to construct a new version of the humble brewer's yeast, Saccharomyces cerevisiae. Each year, the Sc2.0 consortium gather to discuss progress in this ambitious project and highlight new developments at the fore...
journal_title:ACS synthetic biology
pub_type: 杂志文章,评审
doi:10.1021/acssynbio.6b00227
更新日期:2016-09-16 00:00:00
abstract::Multidrug resistance (MDR) is a globally relevant problem that requires novel approaches. Two-component systems are a promising, yet untapped target for novel antibacterials. They are prevalent in bacteria and absent in mammals, and their activity can be modulated upon perception of various stimuli. Screening pre-exis...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00288
更新日期:2017-07-21 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::Microbial mutualisms play critical roles in a diverse number of ecosystems and have the potential to improve the efficiency of bioproduction for desirable chemicals. We investigate the growth of a photosynthetic cyanobacterium, Synechococcus elongatus PCC 7942, and a diazotroph, Azotobacter vinelandii, in coculture. F...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00107
更新日期:2016-09-16 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::In this paper, we present a new strategy for microprinting dense bacterial communities with a prescribed organization on a substrate. Unlike conventional bioprinting techniques that require bioinks, through optogenetic manipulation, we directly manipulated the behaviors of Pseudomonas aeruginosa to allow these living ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00003
更新日期:2018-05-18 00:00:00