Abstract：
:Successful redirection of endogenous resources into heterologous pathways is a central tenet in the creation of efficient microbial cell factories. This redirection, however, may come at a price of poor biomass accumulation, reduced cofactor regeneration and low recombinant enzyme expression. In this study, we propose a metabolite valve to mitigate these issues by dynamically tuning endogenous processes to balance the demands of cell health and pathway efficiency. A control node of glucose utilization, glucokinase (Glk), was exogenously manipulated through either engineered antisense RNA or an inverting gene circuit. Using these techniques, we were able to directly control glycolytic flux, reducing the specific growth rate of engineered Escherichia coli by up to 50% without altering final biomass accumulation. This modulation was accompanied by successful redirection of glucose into a model pathway leading to an increase in the pathway yield and reduced carbon waste to acetate. This work represents one of the first examples of the dynamic redirection of glucose away from central carbon metabolism and enables the creation of novel, efficient intracellular pathways with glucose used directly as a substrate.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Solomon KV,Sanders TM,Prather KLdoi
10.1016/j.ymben.2012.08.006subject
Has Abstractpub_date
2012-11-01 00:00:00pages
661-71issue
6eissn
1096-7176issn
1096-7184pii
S1096-7176(12)00095-Xjournal_volume
14pub_type
杂志文章abstract：:Synthesis of polyketides at high titer and yield is important for producing pharmaceuticals and biorenewable chemical precursors. In this work, we engineered cofactor and transport pathways in Saccharomyces cerevisiae to increase acetyl-CoA, an important polyketide building block. The highly regulated yeast pyruvate d...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.02.009
更新日期：2016-07-01 00:00:00
abstract：:3-Ketosteroid-△(1)-dehydrogenase (KstD) is a key enzyme involved in the microbial catabolism of sterols. Here, three homologues of KstD were characterized from Mycobacterium neoaurum ATCC 25795, showing distinct substrate preferences and transcriptional responses to steroids. Single deletion of any MN-kstD failed to r...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.05.005
更新日期：2014-07-01 00:00:00
abstract：:Ethyl acetate is an industrially relevant ester that is currently produced exclusively through unsustainable processes. Many yeasts are able to produce ethyl acetate, but the main responsible enzyme has remained elusive, hampering the engineering of novel production strains. Here we describe the discovery of a new enz...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.03.004
更新日期：2017-05-01 00:00:00
abstract：:Caffeic acid has been widely recognized as a versatile pharmacophore for synthesis of new chemical entities, among which caffeic acid derived phenethyl esters and amides are the most extensively-investigated bioactive compounds with potential therapeutical applications. However, the natural biosynthetic routes for caf...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.09.011
更新日期：2017-11-01 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：: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：:Previous work in our laboratories investigated the use of methyl alpha-glucoside (alpha-MG), a glucose analog that shares a phosphotransferase system with glucose, to modulate glucose uptake and therefore reduce acetate accumulation. The results of that study showed a significant improvement in batch culture performan...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.1999.0141
更新日期：2000-04-01 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：:Numerous value-added chemicals can be produced using xylan as a feedstock. However, the product yields are limited by low xylan utilization efficiency, as well as by carbon flux competition between biomass production and biosynthesis. Herein, a dynamic consolidated bioprocessing strategy was developed, which coupled x...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.04.001
更新日期：2020-07-01 00:00:00
abstract：:One of the challenges in strain improvement by evolutionary engineering is to subsequently determine the molecular basis of the improved properties that were enriched from the natural genetic variation during the selective conditions. This study focuses on Saccharomyces cerevisiae IMS0002 which, after metabolic and ev...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2010.08.003
更新日期：2010-11-01 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：:(13)C metabolic flux analysis (MFA) has become an important and powerful tool for the quantitative analysis of metabolic networks in the framework of metabolic engineering. Isotopically instationary (13)C MFA under metabolic stationary conditions is a promising refinement of classical stationary MFA. It accounts for t...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.05.006
更新日期：2006-11-01 00:00:00
abstract：:One of the key drivers for successful metabolic engineering in microbes is the efficacy by which genomes can be edited. As such there are many methods to choose from when aiming to modify genomes, especially those of model organisms like yeast and bacteria. In recent years, clustered regularly interspaced palindromic ...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2015.12.003
更新日期：2016-03-01 00:00:00
abstract：:Aromatic amino acids are precursors of numerous plant secondary metabolites with diverse biological functions. Many of these secondary metabolites are already being used as active pharmaceutical or nutraceutical ingredients, and there are numerous exploratory studies of other compounds with promising applications. p-C...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.08.003
更新日期：2015-09-01 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：:Selective estrogen receptor (ER) modulators are highly successful breast cancer therapies, but they are not effective in patients with ER negative and selective estrogen receptor modulator (SERM)-resistant tumors. Understanding the mechanisms of estrogen-stimulated proliferation may provide a route to design estrogen-...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.06.005
更新日期：2006-11-01 00:00:00
abstract：:Muconic acid (MA) is a dicarboxylic acid used for the production of industrially relevant chemicals such as adipic acid, terephthalic acid, and caprolactam. Because the synthesis of these polymer precursors generates toxic intermediates by utilizing petroleum-derived chemicals and corrosive catalysts, the development ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.02.002
更新日期：2018-03-01 00:00:00
abstract：:Stress hormones and pro-inflammatory cytokines are putative signals triggering increased energy expenditure or "hypermetabolism" commonly observed in inflammatory states. Cytokines also cause the release of reactive oxidants by immune cells resident in tissues in vivo. Therefore, we hypothesized that oxidative stress ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/s1096-7176(03)00042-9
更新日期：2003-10-01 00:00:00
abstract：:Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells. Previous attempts to culture hepatocytes in plasma yielded poor functional results. Recently we reported that hormone (insulin and hydrocortisone) and amino acid supplementation redu...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/s1096-7176(02)00011-3
更新日期：2003-01-01 00:00:00
abstract：:To synthesize glycerol, a major by-product during anaerobic production of ethanol, the yeast Saccharomyces cerevisiae would consume up to 4% of the sugar feedstock in typical industrial ethanol processes. The present study was dedicated to decreasing the glycerol production mostly in industrial ethanol producing yeast...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2010.11.003
更新日期：2011-01-01 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：: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：:A novel strategy to finely control a large metabolic flux by using a "metabolic transistor" approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.01.002
更新日期：2015-03-01 00:00:00
abstract：:A 2D-NMR method based on zero-quantum filtered (ZQF-) TOtal Correlation SpectroscopY (TOCSY) was applied to measure 13C-enrichments in complex mixtures of 13C-labeled metabolites generated in carbon-labeling experiments. Using ZQF-TOCSY, more than 30 13C-enrichments could be potentially measured from the analysis of a...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.03.001
更新日期：2007-05-01 00:00:00
abstract：:Genetic manipulation in cyanobacteria enables the direct production of valuable chemicals from carbon dioxide. However, there are still very few reports of the production of highly effective photosynthetic chemicals. Several synthetic metabolic pathways (e.g., isopropanol, acetone, isoprene, and fatty acids) have been...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2019.07.012
更新日期：2020-01-01 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：:This paper presents a new mathematical framework for modeling of in vivo dynamics and for metabolic re-design: the linlog approach. This approach is an extension of metabolic control analysis (MCA), valid for large changes of enzyme and metabolite levels. Furthermore, the presented framework combines MCA with kinetic ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/s1096-7176(03)00025-9
更新日期：2003-07-01 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：: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：: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
