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 modeling, thereby also combining the merits of both approaches. The linlog framework includes general expressions giving the steady-state fluxes and metabolite concentrations as a function of enzyme levels and extracellular concentrations, and a metabolic design equation that allows direct calculation of required enzyme levels for a desired steady state when control and response coefficients are available. Expressions giving control coefficients as a function of the enzyme levels are also derived. The validity of the linlog approximation in metabolic modeling is demonstrated by application of linlog kinetics to a branched pathway with moiety conservation, reversible reactions and allosteric interactions. Results show that the linlog approximation is able to describe the non-linear dynamics of this pathway very well for concentration changes up to a factor 20. Also the metabolic design equation was tested successfully.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Visser D,Heijnen JJdoi
10.1016/s1096-7176(03)00025-9subject
Has Abstractpub_date
2003-07-01 00:00:00pages
164-76issue
3eissn
1096-7176issn
1096-7184pii
S1096717603000259journal_volume
5pub_type
杂志文章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：: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：: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：: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：: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：:Whereas microbial fermentation processes for producing ethanol and related alcohol biofuels are well established, biodiesel (methyl esters of fatty acids) is exclusively derived from plant oils. Slow cycle times for engineering oilseed metabolism and the excessive accumulation of glycerol as a byproduct are two major ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2008.08.006
更新日期：2008-11-01 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：: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：: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：:The glycolipid synthase MG517 from Mycoplasma genitalium catalyzes the glucosyl transfer from UDPGlc to diacylglycerol producing glycoglycerolipids (GGL) (Andrés et al., 2011). The enzyme was functional in E. coli accumulating GGL in the plasma membrane. A metabolic engineering strategy for GGL production was evaluate...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.06.001
更新日期：2012-09-01 00:00:00
abstract：:Optimizing the productivity of bioengineered strains requires balancing ATP generation and carbon atom conservation through fine-tuning cell respiration and metabolism. Traditional approaches manipulate cell respiration by altering air feeding, which are technically difficult especially in large bioreactors. An approa...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2011.09.006
更新日期：2011-11-01 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：:Pigmented metabolites have great potential for use in biosensors that target low-resource areas, since sensor output can be interpreted without any equipment. However, full repression of pigment production when undesired is challenging, as even small amounts of enzyme can catalyze the production of large, visible amou...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.07.004
更新日期：2017-09-01 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：:High titer 1-butanol production in Escherichia coli has previously been achieved by overexpression of a modified clostridial 1-butanol production pathway and subsequent deletion of native fermentation pathways. This strategy couples growth with production as 1-butanol pathway offers the only available terminal electro...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.04.003
更新日期：2017-05-01 00:00:00
abstract：:Hydrocortisone is an effective anti-inflammatory drug and also an important intermediate for synthesis of other steroid drugs. The filamentous fungus Absidia orchidis is renowned for biotransformation of acetylated cortexolone through 11β-hydroxylation to produce hydrocortisone. However, due to the presence of 11α-hyd...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2019.10.006
更新日期：2020-01-01 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：:Biotin is an archetypal vitamin used as cofactor for carboxylation reactions found in all forms of life. However, biotin biosynthesis is an elaborate multi-enzymatic process and metabolically costly. Moreover, many industrially relevant organisms are incapable of biotin synthesis resulting in the requirement to supple...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.12.013
更新日期：2017-03-01 00:00:00
abstract：:Fucosyllactoses (FLs), present in human breast milk, have been reported to benefit human health immensely. Especially, 3-fucosyllactose (3-FL) has numerous benefits associated with a healthy gut ecosystem. Metabolic engineering of microorganisms is thought to be currently the only option to provide an economically fea...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.05.021
更新日期：2018-07-01 00:00:00
abstract：:Two types of non-homologous beta-carotene ketolases (CrtW and CrtO) were previously described. We report improvement of a CrtO-type of beta-carotene ketolase for canthaxanthin production in a methylotrophic bacterium, Methylomonas sp. 16a, which could use the C1 substrate (methane or methanol) as sole carbon and energ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.05.004
更新日期：2007-07-01 00:00:00
abstract：:An engineered reversal of the β-oxidation cycle (r-BOX) and the fatty acid biosynthesis (FAB) pathway are promising biological platforms for advanced fuel and chemical production in part due to their iterative nature supporting the synthesis of various chain length products. While diverging in their carbon-carbon elon...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.11.003
更新日期：2018-01-01 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：:The intracellular redox state plays an important role in the cellular physiology that determines the efficiency of chemical and biofuel production by microbial cell factories. However, it is difficult to achieve optimal redox rebalancing of synthetic pathways owing to the sensitive responses of cellular physiology acc...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2013.09.003
更新日期：2013-11-01 00:00:00
abstract：:Lipogenic organisms provide an ideal platform for biodiesel and oleochemical production. Through our previous rational metabolic engineering efforts, lipogenesis titers in Yarrowia lipolytica were significantly enhanced. However, the resulting strain still suffered from decreased biomass generation rates. Here, we emp...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.02.003
更新日期：2015-05-01 00:00:00
abstract：:A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information e...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/s1096-7176(03)00023-5
更新日期：2003-04-01 00:00:00
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：: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：:In this report, UbiE and UbiH in the quinone modification pathway (QMP) were identified in addition to UbiG as bottleneck enzymes in the CoQ10 biosynthesis by Rhodobacter sphaeroides. The CoQ10 content was enhanced after co-overexpression of UbiE and UbiG, however, accompanied by the accumulation of the intermediate 1...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.03.012
更新日期：2015-05-01 00:00:00
abstract：:Directed molecular evolution is a recursive process of controlled genetic diversification and functional screening. The success of this approach is dependent on both the quality of the genetic diversity and the ability to accurately screen a large population of individual genetic variants for those having improved fun...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2004.09.001
更新日期：2005-01-01 00:00:00
abstract：:Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulat...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.06.002
更新日期：2017-07-01 00:00:00
