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 evolved such that they are intrinsically robust in their network structure. In this article, we presented Ensemble Modeling for Robustness Analysis (EMRA), which combines a continuation method with the Ensemble Modeling approach, for investigating the robustness issue of non-native pathways. EMRA investigates a large ensemble of reference models with different parameters, and determines the effects of parameter drifting until a bifurcation point, beyond which a stable steady state disappears and system failure occurs. A pathway is considered to have high bifurcational robustness if the probability of system failure is low in the ensemble. To demonstrate the utility of EMRA, we investigate the bifurcational robustness of two synthetic central metabolic pathways that achieve carbon conservation: non-oxidative glycolysis and reverse glyoxylate cycle. With EMRA, we determined the probability of system failure of each design and demonstrated that alternative designs of these pathways indeed display varying degrees of bifurcational robustness. Furthermore, we demonstrated that target selection for flux improvement should consider the trade-offs between robustness and performance.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Lee Y,Lafontaine Rivera JG,Liao JCdoi
10.1016/j.ymben.2014.06.006subject
Has Abstractpub_date
2014-09-01 00:00:00pages
63-71eissn
1096-7176issn
1096-7184pii
S1096-7176(14)00087-1journal_volume
25pub_type
杂志文章abstract：:3-Hydroxypropionic acid (3-HP) is an attractive platform chemical, which can be used to produce a variety of commodity chemicals, such as acrylic acid and acrylamide. For enabling a sustainable alternative to petrochemicals as the feedstock for these commercially important chemicals, fermentative production of 3-HP is...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.01.005
更新日期：2014-03-01 00:00:00
abstract：:5-Aminovalerate (5AVA) is the precursor of valerolactam, a potential building block for producing nylon 5, and is a C5 platform chemical for synthesizing 5-hydroxyvalerate, glutarate, and 1,5-pentanediol. Escherichia coli was metabolically engineered for the production of 5-aminovalerate (5AVA) and glutarate. When the...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.11.011
更新日期：2013-03-01 00:00:00
abstract：:In this report, we identify the relevant factors to increase production of medium chain n-alcohols through an expanded view of the reverse β-oxidation pathway. We began by creating a base strain capable of producing medium chain n-alcohols from glucose using a redox-balanced and growth-coupled metabolic engineering st...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.05.011
更新日期：2018-07-01 00:00:00
abstract：:The complete genome sequence of the filamentous fungi Aspergillus nidulans has paved the way for fundamental research on this industrially important species. To the best of our knowledge, this is the first time a gene encoding for ATP-dependent NADH kinase (ATP:NADH 2'-phosphotransferase, EC 2.7.1.86) has been identif...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2008.08.008
更新日期：2009-01-01 00:00:00
abstract：:β-Oxidation is the ubiquitous metabolic strategy to break down fatty acids. In the course of this four-step process, two carbon atoms are liberated per cycle from the fatty acid chain in the form of acetyl-CoA. However, typical β-oxidative strategies are not restricted to monocarboxylic (fatty) acid degradation only, ...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2017.05.004
更新日期：2017-07-01 00:00:00
abstract：:Metabolic flux analysis is a useful tool to analyze cell metabolism. In this study, we report the use of a metabolic model with 34 fluxes to study the 293 cell, in order to improve its growth capacity in a DMEM/F12 medium. A batch, fed-batch with glutamine feeding, fed-batch with essential amino acids, and finally a f...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.2000.0152
更新日期：2000-10-01 00:00:00
abstract：:This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and fi...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.01.001
更新日期：2012-03-01 00:00:00
abstract：:Succinic acid is a platform chemical of recognized industrial value and accordingly faces a continuous challenge to enable manufacturing from most attractive raw materials. It is mainly produced from glucose, using microbial fermentation. Here, we explore and optimize succinate production from sucrose, a globally appl...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.10.003
更新日期：2017-11-01 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：:13C metabolic flux analysis (13C-MFA) is a widely used tool for quantitative analysis of microbial and mammalian metabolism. Until now, 13C-MFA was based mainly on measurements of isotopic labeling of amino acids derived from hydrolyzed biomass proteins and isotopic labeling of extracted intracellular metabolites. Her...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.06.007
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND:6-Methylsalicylic acid synthase (MSAS), a fungal polyketide synthase from Penicillium patulum, is perhaps the simplest polyketide synthase that embodies several hallmarks of this family of multifunctional enzymes--a large multidomain protein, a high degree of specificity toward acetyl-CoA and malonyl-CoA sub...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.1999.0113
更新日期：1999-04-01 00:00:00
abstract：:Metabolic Engineering offers an opportunity to forge a link between metabolic physiologists, working with mammalian systems and metabolic engineers. Many parallels may be drawn between the specific modification of metabolic networks to improve cellular properties and the analysis of metabolic networks in search of cau...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2003.10.008
更新日期：2004-01-01 00:00:00
abstract：:Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. Currently, industrial production of simvastatin acid (SVA) is a multistep process starting from the natural product lovastatin. For this reason, there is significant interest in direct production of simvasta...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.09.005
更新日期：2019-01-01 00:00:00
abstract：:Having previously introduced the mathematical framework of topological metabolic analysis (TMA) - a novel optimization-based technique for modeling metabolic networks of arbitrary size and complexity - we demonstrate how TMA facilitates unique methods of metabolic interrogation. With the aid of several hybridoma metab...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2010.12.003
更新日期：2011-03-01 00:00:00
abstract：:Styrene is an important petroleum-derived molecule that is polymerized to make versatile plastics, including disposable silverware and foamed packaging materials. Finding more sustainable methods, such as biosynthesis, for producing styrene is essential due to the increasing severity of climate change as well as the l...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.05.009
更新日期：2020-09-01 00:00:00
abstract：:We observed that removing pantothenate (vitamin B5), a precursor to co-enzyme A, from the growth medium of Saccharomyces cerevisiae engineered to produce β-farnesene reduced the strain׳s farnesene flux by 70%, but increased its viability, growth rate and biomass yield. Conversely, the growth rate and biomass yield of ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.07.006
更新日期：2014-09-01 00:00:00
abstract：:Cell metabolism is an important platform for sustainable biofuel, chemical and pharmaceutical production but its complexity presents a major challenge for scientists and engineers. Although in silico strains have been designed in the past with predicted performances near the theoretical maximum, real-world performance...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.11.013
更新日期：2015-03-01 00:00:00
abstract：:A large number of CHO glycosylation mutants were isolated by Ricinus communis agglutinin-I (RCA-I). Complementation tests revealed that all these mutant lines possessed a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. Sequencing analyses on the GnT I cDNAs isolated from 16 mutant lines led to the identi...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2010.03.002
更新日期：2010-07-01 00:00:00
abstract：:Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2011.09.008
更新日期：2011-11-01 00:00:00
abstract：:As synthetic pathways built from exogenous enzymes become more complicated, the probability of encountering undesired interactions with host organisms increases, thereby lowering product titer. An emerging strategy to combat this problem is to spatially organize pathway enzymes into multi-protein complexes, where high...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2011.09.003
更新日期：2012-05-01 00:00:00
abstract：:Global gene regulation throughout the Escherichia coli stress response to overexpression of each of five recombinant proteins was evaluated. Reverse-transcriptase polymerase chain reaction-amplified mRNA from induced and control cells were hybridized with a DNA array of Kohara clones representing 16% (700 genes) of th...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.2000.0148
更新日期：2000-07-01 00:00:00
abstract：:Klebsiella oxytoca KMS005 (∆adhE∆ackA-pta∆ldhA) was metabolically engineered to improve 2,3-butanediol (BDO) yield. Elimination of alcohol dehydrogenase E (adhE), acetate kinase A-phosphotransacetylase (ackA-pta), and lactate dehydrogenase A (ldhA) enzymes allowed BDO production as a primary pathway for NADH re-oxidat...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.04.004
更新日期：2015-07-01 00:00:00
abstract：:Intense synthesis of proteins and chemicals in engineered microbes impose metabolic burden, frequently leading to reduced growth and heterogeneous cell population. Thus, the correct balance between growth and production is important. Such balance can be engineered through dynamic control of pathways, but few broadly a...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.03.012
更新日期：2020-09-01 00:00:00
abstract：:In this study strains of Ralstonia eutropha H16 and Pseudomonas putida KT2440 were engineered which are suitable for biotechnological production of 2-methylcitric acid (2MC). Analysis of a previous mutant of R. eutropha able to accumulate 2MC recommended this strain as a candidate for fermentative production of 2MC. T...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.05.007
更新日期：2006-11-01 00:00:00
abstract：:Saccharomyces cerevisiae is an efficient host for natural-compound production and preferentially employed in academic studies and bioindustries. However, S. cerevisiae exhibits limited production capacity for lipophilic natural products, especially compounds that accumulate intracellularly, such as polyketides and car...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.11.009
更新日期：2019-03-01 00:00:00
abstract：:Cyanobacteria can be exploited as photosynthetic platforms for heterologous generation of terpene hydrocarbons with industrial applications. Transformation of Synechocystis and heterologous expression of the β-phellandrene synthase (PHLS) gene alone is necessary and sufficient to confer to Synechocystis the ability to...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.09.010
更新日期：2015-11-01 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：:Utilization of Candida glabrata overproducing pyruvate is a promising strategy for high-level acetoin production. Based on the known regulatory and metabolic information, acetaldehyde and thiamine were fed to identify the key nodes of carboligase activity reaction (CAR) pathway and provide a direction for engineering ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2013.12.005
更新日期：2014-03-01 00:00:00
abstract：:We generated a genomic library from sheared Clostridium acetobutylicum ATCC 824 DNA, whereby inserts can be expressed in both directions from the thiolase promoter, P(thl). Serial transfer of library-bearing C. acetobutylicum cultures exposed to increasing butyrate concentrations enriched for inserts containing fragme...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2009.12.004
更新日期：2010-05-01 00:00:00
abstract：:Discovery of the cold-inducible RNA-binding protein (CIRP) in mouse fibroblasts suggests that growth suppression at hypothermic conditions is due to an active response by the cell rather than due to passive thermal effects. To determine the effect of down-regulated CIRP expression on cell growth and erythropoietin (EP...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.11.003
更新日期：2007-03-01 00:00:00
