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 is often sub-optimal. Here, we simulate how strain performance is impacted when subjected to many randomly varying perturbations, including discrepancies between gene expression and in vivo flux, osmotic stress, and substrate uptake perturbations due to concentration gradients in bioreactors. This computational study asks whether robust performance can be achieved by adopting robustness-enhancing mechanisms from naturally evolved organisms-in particular, redundancy. Our study shows that redundancy, typically perceived as a ubiquitous robustness-enhancing strategy in nature, can either improve or undermine robustness depending on the magnitude of the perturbations. We also show that the optimal number of redundant pathways used can be predicted for a given perturbation size.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Yang L,Srinivasan S,Mahadevan R,Cluett WRdoi
10.1016/j.ymben.2014.11.013subject
Has Abstractpub_date
2015-03-01 00:00:00pages
114-122eissn
1096-7176issn
1096-7184pii
S1096-7176(14)00163-3journal_volume
28pub_type
杂志文章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：:We present a model-based method, designated Inverse Metabolic Control Analysis (IMCA), which can be used in conjunction with classical Metabolic Control Analysis for the analysis and design of cellular metabolism. We demonstrate the capabilities of the method by first developing a comprehensively curated kinetic model...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.04.002
更新日期：2016-09-01 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：:Oleaginous yeasts are valuable systems for biosustainable production of hydrocarbon-based chemicals. Yarrowia lipolytica is one of the best characterized of these yeast with respect to genome annotation and flux analysis of metabolic processes. Nonetheless, progress is hampered by a dearth of genome-wide tools enablin...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.05.008
更新日期：2018-07-01 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：:Natural products are a rich source of potential drugs for many applications. Discovery of natural products through the activation of cryptic gene clusters encoding their biosynthetic pathways, engineering of those biosynthetic pathways and optimization of production yields often rely on the expression of these gene cl...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.09.004
更新日期：2018-09-01 00:00:00
abstract：:We report improved NADPH flux and xylitol biosynthesis in engineered E. coli. Xylitol is produced from xylose via an NADPH dependent reductase. We utilize 2-stage dynamic metabolic control to compare two approaches to optimize xylitol biosynthesis, a stoichiometric approach, wherein competitive fluxes are decreased, a...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2021.01.005
更新日期：2021-01-16 00:00:00
abstract：:Methanol is a promising feedstock for bioproduction of fuels and chemicals, thus massive efforts have been devoted to engineering non-native methylotrophic platform microorganisms to utilize methanol. Herein, we rationally designed and experimentally engineered the industrial workhorse Corynebacterium glutamicum to se...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.07.011
更新日期：2018-09-01 00:00:00
abstract：:Increasing the microbial CO2-fixing efficiency often requires supplying sufficient ATP and redirecting carbon flux for the production of metabolites. However, addressing these two issues concurrently remains a challenge. Here, we present a combinational strategy based on a synergetic CO2-fixing pathway that combines a...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.05.007
更新日期：2018-05-01 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：: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：: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：:Improved supply of farnesyl diphosphate (FPP) is often considered as a typical strategy for engineering Saccharomyces cerevisiae towards efficient terpenoid production. However, in the engineered strains with enhanced precursor supply, the production of the target metabolite is often impeded by insufficient capacity o...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.04.009
更新日期：2015-07-01 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：: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：: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：:Pyocyanin is a secondary metabolite from Pseudomonas aeruginosa that belongs to the class of phenazines, which are aromatic nitrogenous compounds with numerous biological functions. Besides its antifungal and antimicrobial activities, pyocyanin is a remarkable redox-active molecule with potential applications ranging ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2021.01.002
更新日期：2021-01-14 00:00:00
abstract：:Punicic acid (PuA; 18:3Δ9cis,11trans,13cis), a conjugated linolenic acid isomer bearing three conjugated double bonds, is associated with various health benefits and has potential for industrial use. The major nature source of this unusual fatty acid is pomegranate (Punica granatum) seed oil, which contains up to 80% ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.08.011
更新日期：2020-11-01 00:00:00
abstract：:A Chinese hamster ovary (CHO) cell line producing recombinant human bone morphogenetic protein-4 (rhBMP-4) (CHO-BMP-4), which expresses essential components of BMP signal transduction, underwent autocrine BMP-4 signaling. RNA seq analysis on CHO host cells (DG44) treated with rhBMP-4 (20 µg/mL) suggested that rhBMP-4 ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.11.003
更新日期：2019-03-01 00:00:00
abstract：:The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers a...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2012.04.006
更新日期：2012-07-01 00:00:00
abstract：:Metabolic engineering is the directed improvement of cellular properties through the modification of specific biochemical reactions or the introduction of new ones, with the use of recombinant DNA technology. As such, metabolic engineering emphasizes metabolic pathway integration and relies on metabolic fluxes as dete...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1006/mben.1998.0101
更新日期：1999-01-01 00:00:00
abstract：:Isotopically nonstationary metabolic flux analysis (INST-MFA) provides a versatile platform to quantitatively assess in vivo metabolic activities of autotrophic systems. By applying INST-MFA to recombinant aldehyde-producing cyanobacteria, we identified metabolic alterations that correlated with increased strain perfo...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.03.007
更新日期：2020-07-01 00:00:00
abstract：:Predicting resource allocation between cell processes is the primary step towards decoding the evolutionary constraints governing bacterial growth under various conditions. Quantitative prediction at genome-scale remains a computational challenge as current methods are limited by the tractability of the problem or by ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.10.003
更新日期：2015-11-01 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：:Metabolic engineering is used to improve titers, yields and generation rates for biochemical products in host microbes such as Escherichia coli. A wide range of biochemicals are derived from the central carbon metabolite acetyl-CoA, and the largest native drain of acetyl-CoA in most microbes including E. coli is entry...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.06.006
更新日期：2020-09-01 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：:Anthocyanins are widely distributed, glycosylated, water-soluble plant pigments, which give many fruits and flowers their red, purple or blue colouration. Their beneficial effects in a dietary context have encouraged increasing use of anthocyanins as natural colourants in the food and cosmetic industries. However, the...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.06.004
更新日期：2018-07-01 00:00:00
abstract：:Valine, which is one of the branched-chain amino acids (BCAAs) essential for humans, is widely used in animal feed, dietary supplements and pharmaceuticals. At the commercial level, valine is usually produced by bacterial fermentation from glucose. However, valine biosynthesis can also proceed in the yeast Saccharomyc...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.02.011
更新日期：2018-03-01 00:00:00
abstract：:An innovative "biodrug" concept based on oral administration of living recombinant microorganisms as a vehicle to deliver active compounds directly into the digestive tract has recently been developed. To validate this concept, we studied a recombinant Saccharomyces cerevisiae strain in order to investigate its viabil...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2009.01.001
更新日期：2009-05-01 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
