Abstract：
:The design of synthetic cells requires a detailed understanding of the relevance of genes and gene networks underlying complex cellular phenotypes. Transposon-sequencing (Tn-seq) and constraint-based metabolic modeling can be used to probe the core genetic and metabolic networks underlying a biological process. Integrating these highly complementary experimental and in silico approaches has the potential to yield a highly comprehensive understanding of the core networks of a cell. Specifically, it can facilitate the interpretation of Tn-seq data sets and identify gaps in the data that could hinder the engineering of the cellular system, while also providing refined models for the accurate predictions of cellular metabolism. Here, we present Tn-Core, the first easy-to-use computational pipeline specifically designed for integrating Tn-seq data with metabolic modeling, prepared for use by both experimental and computational biologists. Tn-Core is a MATLAB toolbox that contains several custom functions, and it is built upon existing functions within the COBRA Toolbox and the TIGER Toolbox. Tn-Core takes as input a genome-scale metabolic model, Tn-seq data, and optionally RNA-seq data, and returns: (i) a context-specific core metabolic model; (ii) an evaluation of redundancies within core metabolic pathways, and optionally (iii) a refined genome-scale metabolic model. A simple, user-friendly workflow, requiring limited knowledge of metabolic modeling, is provided that allows users to run the analyses and export the data as easy-to-explore files of value to both experimental and computational biologists. We demonstrate the utility of Tn-Core using Sinorhizobium meliloti, Pseudomonas aeruginosa, and Rhodobacter sphaeroides genome-scale metabolic reconstructions as case studies.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
diCenzo GC,Mengoni A,Fondi Mdoi
10.1021/acssynbio.8b00432subject
Has Abstractpub_date
2019-01-18 00:00:00pages
158-169issue
1issn
2161-5063journal_volume
8pub_type
杂志文章abstract：:Phages are biological entities found in every ecosystem. Although much has been learned about them in past decades, significant knowledge gaps remain. Manipulating virulent phage genomes is challenging. To date, no efficient gene-editing tools exist for engineering virulent lactococcal phages. Lactococcus lactis is a ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00388
更新日期：2017-07-21 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：: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：: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：:Eukaryotic transcriptional factors (TFs) typically recognize short genomic sequences alone or together with other proteins to modulate gene expression. Mapping of TF-DNA interactions in the genome is crucial for understanding the gene regulatory programs in cells. While chromatin immunoprecipitation followed by sequen...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00358
更新日期：2017-06-16 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
doi：10.1021/sb400156v
更新日期：2014-07-18 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：:It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspire...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500233u
更新日期：2015-02-20 00:00:00
abstract：:Cell-free gene expression systems are emerging as an important platform for a diverse range of synthetic biology and biotechnology applications, including production of robust field-ready biosensors. Here, we combine programmed cellular autolysis with a freeze-thaw or freeze-dry cycle to create a practical, reproducib...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00253
更新日期：2017-12-15 00:00:00
abstract：:The engineering of microbial metabolic pathways over the last two decades has led to numerous examples of cell factories used for the production of small molecules. These molecules have an array of utility in commercial industries and as in situ expressed biomarkers or therapeutics in microbial applications. While mos...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00497
更新日期：2021-01-15 00:00:00
abstract：:Synonymous mutation of the N-terminal coding sequence (NCS) has been used to regulate gene expression. We here developed a statistical model to predict the effect of the NCSs on protein expression in Bacillus subtilis WB600. First, a synonymous mutation was performed within the first 10 residues of a superfolder green...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00309
更新日期：2021-01-19 00:00:00
abstract：:Light-switchable proteins enable unparalleled control of molecular biological processes in live organisms. Previously, we have engineered red/far-red and green/red photoreversible two-component signal transduction systems (TCSs) with transcriptional outputs in E. coli and used them to characterize and control syntheti...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500273n
更新日期：2014-11-21 00:00:00
abstract：:Whole cell biosensors are genetic systems that link the presence of a chemical, or other stimulus, to a user-defined gene expression output for applications in sensing and control. However, the gene expression level of biosensor regulatory components required for optimal performance is nonintuitive, and classical iter...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00448
更新日期：2020-03-20 00:00:00
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 l...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500222z
更新日期：2014-09-19 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：: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：:To spatially control biochemical functions at specific sites within a genome, we have engineered a synthetic switch that activates when bound to its DNA target site. The system uses two CRISPR-Cas complexes to colocalize components of a de novo-designed protein switch (Co-LOCKR) to adjacent sites in the genome. Coloca...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00012
更新日期：2020-09-18 00:00:00
abstract：:Synthetic biology and metabolic engineering offer potentially green and attractive routes to the production of high value compounds. The provision of high-quality parts and pathways is crucial in enabling the biosynthesis of chemicals using synthetic biology. While a number of regulatory parts that provide control at ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00375
更新日期：2020-10-16 00:00:00
abstract：:Robust and precise ratio control of heterogeneous phenotypes within an isogenic population is an essential task, especially in the development and differentiation of a large number of cells such as bacteria, sensory receptors, and blood cells. However, the mechanisms of such ratio control are poorly understood. Here, ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00030
更新日期：2019-06-21 00:00:00
abstract：:Bacterial microcompartments are subcellular compartments found in many prokaryotes; they consist of a protein shell that encapsulates enzymes that perform a variety of functions. The shell protects the cell from potentially toxic intermediates and colocalizes enzymes for higher efficiency. Accordingly, it is of consid...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00011
更新日期：2019-04-19 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：:Erythromycin is necessary in medical treatment and known to be biosynthesized with propionyl-CoA as direct precursor. Oversupply of propionyl-CoA induced hyperpropionylation, which was demonstrated as harmful for erythromycin synthesis in Saccharopolyspora erythraea. Herein, we identified three propionyl-CoA synthetas...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00396
更新日期：2019-02-15 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：:Menthol isomers are high-value monoterpenoid commodity chemicals, produced naturally by mint plants, Mentha spp. Alternative clean biosynthetic routes to these compounds are commercially attractive. Optimization strategies for biocatalytic terpenoid production are mainly focused on metabolic engineering of the biosynt...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00092
更新日期：2015-10-16 00:00:00
abstract：:Biosensors regulated by specific substrates are needed to develop genetic tools to meet the needs of engineering microbial cell factories. Here, a xylose-inducible biosensor (xylbiosensor), comprising the Escherichia coli activation factor XylR, fusion activation domain (AD) VPRH, and a hybrid promoter with operator x...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00122
更新日期：2020-05-15 00:00:00
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：:There is a growing interest in mediating information transfer between biology and electronics. By the addition of redox mediators to various samples and cells, one can both electronically obtain a redox "portrait" of a biological system and, conversely, program gene expression. Here, we have created a cell-based synth...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00469
更新日期：2020-05-15 00:00:00
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...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb3000639
更新日期：2012-10-19 00:00:00
abstract：:The ability to rapidly design, build, and test prototypes is of key importance to every engineering discipline. DNA assembly often serves as a rate limiting step of the prototyping cycle for synthetic biology. Recently developed DNA assembly methods such as isothermal assembly and type IIS restriction enzyme systems t...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00060
更新日期：2018-05-18 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
