Abstract：
:One of the main strategies to improve the production of relevant metabolites has been the manipulation of single or multiple key genes in the metabolic pathways. This kind of strategy requires several rounds of experiments to identify enzymes that impact either yield or productivity. The use of mathematical tools to facilitate this process is desirable. In this work, we apply the Ensemble Modeling (EM) framework, which uses phenotypic data (effects of enzyme overexpression or genetic knockouts on the steady-state production rate) to screen for potential models capable of describe existing data and thus gaining insight to improve strains for l-lysine production. Described herein is a strategy to generate a set of kinetic models that describe a set of enzyme overexpression phenotypes previously determined in an Escherichia coli strain that produces increased levels of l-lysine in an industrial laboratory. This final ensemble of models captures the kinetic characteristics of the cell through screening of phenotypes after sequential overexpression of enzymes. Furthermore, these models demonstrate some predictive capability, as starting from the reference producing strain (overexpressing desensitized dihydrodipicolinate synthetase (dapA*)) this set of models is able to predict that the desensitization of aspartate kinase (lysC*) is the next rate-controlling step in the l-lysine pathway. Moreover, this set of models allows for the generation of further targets for testing, for example, phosphoenolpyruvate (Ppc), aspartate aminotransferase (AspC), and glutamate dehydrogenase (GdhA). This work demonstrates the usefulness, applicability, and scope that the Ensemble Modeling framework offers to build production strains.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Contador CA,Rizk ML,Asenjo JA,Liao JCdoi
10.1016/j.ymben.2009.04.002subject
Has Abstractpub_date
2009-07-01 00:00:00pages
221-33issue
4-5eissn
1096-7176issn
1096-7184pii
S1096-7176(09)00036-6journal_volume
11pub_type
杂志文章abstract：:The potential to produce succinate aerobically in Escherichia coli would offer great advantages over anaerobic fermentation in terms of faster biomass generation, carbon throughput, and product formation. Genetic manipulations were performed on two aerobic succinate production systems to increase their succinate yield...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2004.10.003
更新日期：2005-03-01 00:00:00
abstract：:A typical characteristic of the butyric acid-producing Clostridium is coproduction of both butyric and acetic acids. Increasing the butyric acid selectivity important for economical butyric acid production has been rather difficult in clostridia due to their complex metabolic pathways. In this work, Clostridium acetob...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.03.004
更新日期：2014-05-01 00:00:00
abstract：:Using the carbon isotope labeling technique, the response of cyanobacterial central carbon metabolism to the change in environmental conditions was investigated. Synechocystis was grown in the heterotrophic and mixotrophic cultures fed with 13C-labeled glucose. The labeling patterns of the amino acids in biomass hydro...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.2002.0226
更新日期：2002-07-01 00:00:00
abstract：:Although CRISPR-Cas9/Cpf1 have been employed as powerful genome engineering tools, heterologous CRISPR-Cas9/Cpf1 are often difficult to introduce into bacteria and archaea due to their severe toxicity. Since most prokaryotes harbor native CRISPR-Cas systems, genome engineering can be achieved by harnessing these endog...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.03.007
更新日期：2018-05-01 00:00:00
abstract：:Cell culture engineering has to-date used transcriptomic, proteomic, and metabolic flux analyses, attempting to resolve significant questions regarding cell culture performance. Despite the foreseen positive impact, the metabolomic analytical platform has not yet been vastly deployed. Presently, there is no published ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2009.11.001
更新日期：2010-05-01 00:00:00
abstract：:Presented herein is a methodology for quantitatively analyzing the complex signaling network by resorting to colored Petri nets (CPN). The mathematical as well as Petri net models for two basic reaction types were established, followed by the extension to a large signal transduction system stimulated by epidermal grow...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2005.10.001
更新日期：2006-03-01 00:00:00
abstract：:A methionine-producing strain was derived from a lysine-producing Corynebacterium glutamicum through a process of genetic manipulation in order to assess its potential to synthesize and accumulate methionine during growth. The strain carries a deregulated hom gene (hom(FBR)) to abolish feedback inhibition of homoserin...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.05.001
更新日期：2007-07-01 00:00:00
abstract：:The actinomycete Amycolatopsis japonicum is the producer of the chelating compound [S,S]-ethylenediamine-disuccinc acid (EDDS). [S,S]-EDDS is an isomer of ethylenediamine-tetraacetic acid (EDTA), an economically important chelating compound that suffers from an extremely poor degradability. Frequent use of the persist...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.04.003
更新日期：2020-07-01 00:00:00
abstract：:The biological nitrogen fixation carried out by some Bacteria and Archaea is one of the most attractive alternatives to synthetic nitrogen fertilizers. In this study we compared the effect of controlling the maximum activation state of the Azotobacter vinelandii glutamine synthase by a point mutation at the active sit...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.03.002
更新日期：2014-05-01 00:00:00
abstract：:The chemical monomer p-hydroxystyrene (pHS) is used for producing a number of important industrial polymers from petroleum-based feedstocks. In an alternative approach, the microbial production of pHS can be envisioned by linking together a number of different metabolic pathways, of which those based on using glucose ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.01.002
更新日期：2007-05-01 00:00:00
abstract：:β-Nicotinamide mononucleotide (NMN) is, one of the nucleotide compounds, a precursor of NAD+ and has recently attracted attention as a nutraceutical. Here, we develop a whole-cell biocatalyst using Escherichia coli, which enabled selective and effective high production of NMN from the inexpensive feedstock substrates ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.11.008
更新日期：2020-11-18 00:00:00
abstract：:An efficient production process is important for industrial microorganisms. The cellular efficiency of solventogenic clostridia, a group of anaerobes capable of producing a wealth of bulk chemicals and biofuels, must be improved for competitive commercialization. Here, using Clostridium acetobutylicum, a species of so...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.02.006
更新日期：2016-05-01 00:00:00
abstract：:FK506, a widely used immunosuppressant, is produced by industrial fermentation processes using various Streptomyces species. Independently of the strain, structurally related compound FK520 is co-produced, resulting in complex and costly isolation procedures. In this paper, we report a chemobiosynthetic approach for e...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2011.11.003
更新日期：2012-01-01 00:00:00
abstract：:Metabolic pathways in cells must be sufficiently robust to tolerate fluctuations in expression levels and changes in environmental conditions. Perturbations in expression levels may lead to system failure due to the disappearance of a stable steady state. Increasing evidence has suggested that biological networks have...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.06.006
更新日期：2014-09-01 00:00:00
abstract：:Producing some small hydrophobic molecules in microbes is challenging. Often these molecules cannot cross membranes, and thus their production may be limited by lack of storage space in the producing organism. This study reports a new technology for in vivo storage of valuable hydrophobic products in/on biopolymer bod...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.04.006
更新日期：2020-09-01 00:00:00
abstract：:One of the important goals of biology is to understand the relationship between DNA sequence information and nonlinear cellular responses. This relationship is central to the ability to effectively engineer cellular phenotypes, pathways, and characteristics. Expression arrays for monitoring total gene expression based...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.1999.0115
更新日期：1999-10-01 00:00:00
abstract：:Genome-wide or large-scale methodologies employed in functional genomics such as DNA sequencing, transcription profiling, proteomics, and metabolite profiling have become important tools in many metabolic engineering strategies. These techniques allow the identification of genetic differences and insight into their ce...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2003.11.005
更新日期：2004-07-01 00:00:00
abstract：:The rapK gene required for biosynthesis of the DHCHC starter acid that initiates rapamycin biosynthesis was deleted from strain BIOT-3410, a derivative of Streptomyces rapamycinicus which had been subjected to classical strain and process development and capable of robust rapamycin production at titres up to 250mg/L. ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.11.001
更新日期：2013-01-01 00:00:00
abstract：:Increasing the availability of NADPH is commonly used to improve lysine production by Corynebacterium glutamicum since 4 mol of NADPH are required for the synthesis of 1 mol of lysine. Alternatively, engineering of enzymes in lysine synthesis pathway to utilize NADH directly can also be explored for cofactor balance d...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.11.006
更新日期：2019-03-01 00:00:00
abstract：:Fatty acids are the most abundant form of reduced carbon chains available from nature and have diverse uses ranging from food to industrial feedstocks. Plants represent a significant renewable source of fatty acids because many species accumulate them in the form of triacylglycerol as major storage components in seeds...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1006/mben.2001.0204
更新日期：2002-01-01 00:00:00
abstract：:Ginsenoside Rh2 is a potential anticancer drug isolated from medicinal plant ginseng. Fermentative production of ginsenoside Rh2 in yeast has recently been investigated as an alternative strategy compared to extraction from plants. However, the titer was quite low due to low catalytic capability of the key ginseng gly...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.04.009
更新日期：2017-07-01 00:00:00
abstract：:Metabolic engineering technology for industrial microorganisms is under development to create rational, more reliable, and more cost-effective approaches to strain improvement. Strain improvement is a critical component of the drug development process, yet the genetic basis for high production by industrial microorgan...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2004.03.003
更新日期：2004-10-01 00:00:00
abstract：:The construction of large DNA molecules that encode pathways, biological machinery, and entire genomes has been limited to the reproduction of natural sequences. However, now that robust methods for assembling hundreds of DNA fragments into constructs > 20 kb are readily available, optimization of large genetic elemen...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2012.02.005
更新日期：2012-05-01 00:00:00
abstract：:Based on the analysis of molecular interactions of proteins with DNA binding sites, a new approach to developing mathematical models describing gene expression is introduced. Detection of hierarchical structures in metabolic networks can be used to decompose complex reaction schemes. This will be achieved by assigning...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.2000.0175
更新日期：2001-04-01 00:00:00
abstract：:Glucose pulse experiments at seconds time scale resolution were performed in aerobic glucose-limited Escherichia coli chemostat cultures. The dynamic responses of oxygen-uptake and growth rate at seconds time scale were determined using a new method based on the dynamic liquid-phase mass balance for oxygen and the pse...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2011.03.003
更新日期：2011-05-01 00:00:00
abstract：:Dietary carotenoids have been shown to be beneficial to health by decreasing the risk of many diseases. Attempts to enhance carotenoids in food crops have been successful although higher plants appear to resist big changes of carotenoid biosynthesis by metabolic engineering. Here we report the generation of a more nut...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2013.02.005
更新日期：2013-05-01 00:00:00
abstract：:There is considerable interest in mining organisms for new natural products (NPs) and in improving methods to overproduce valuable NPs. Because of the rapid development of tools and strategies for metabolic engineering and the markedly increased knowledge of the biosynthetic pathways and genetics of NP-producing organ...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2018.05.015
更新日期：2018-11-01 00:00:00
abstract：:Development of sustainable biological process for the production of bulk chemicals from renewable feedstock is an important goal of white biotechnology. Ethylene glycol (EG) is a large-volume commodity chemical with an annual production of over 20 million tons, and it is currently produced exclusively by petrochemical...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.10.013
更新日期：2016-01-01 00:00:00
abstract：:Cyanobacteria hold promise as a cell factory for producing biofuels and bio-derived chemicals, but genome engineering of cyanobacteria such as Synechococcus elongatus PCC 7942 poses challenges because of their oligoploidy nature and long-term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA-gui...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.09.006
更新日期：2016-11-01 00:00:00
abstract：:Rational metabolic engineering methods are increasingly employed in designing the commercially viable processes for the production of chemicals relevant to pharmaceutical, biotechnology, and food and beverage industries. With the growing availability of omics data and of methodologies capable to integrate the availabl...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.01.009
更新日期：2016-05-01 00:00:00
