scholarly journals Evolutionary Approaches for Strain Optimization Using Dynamic Models under a Metabolic Engineering Perspective

2009 ◽  
pp. 140-151 ◽  
Author(s):  
Pedro Evangelista ◽  
Isabel Rocha ◽  
Eugénio C. Ferreira ◽  
Miguel Rocha
Keyword(s):  
Metabolic Engineering ◽  
Dynamic Models ◽  
Strain Optimization

Multivariate modular metabolic engineering for pathway and strain optimization

2014 ◽  
Vol 29 ◽  
pp. 156-162 ◽  
Author(s):  
Bradley Walters Biggs ◽  
Brecht De Paepe ◽  
Christine Nicole S Santos ◽  
Marjan De Mey ◽  
Parayil Kumaran Ajikumar
Keyword(s):  
Metabolic Engineering ◽  
Strain Optimization

scholarly journals Complete Biosynthesis of Anthocyanins Using E. coli Polycultures

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
J. Andrew Jones ◽  
Victoria R. Vernacchio ◽  
Shannon M. Collins ◽  
Abhijit N. Shirke ◽  
Yu Xiu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Metabolic Engineering ◽  
Metabolic Pathways ◽  
High Flux ◽  
Chemical Production ◽  
New Paradigm ◽  
Engineering Applications ◽  
Strain Optimization ◽  
Metabolic Burden ◽  
Malonyl Coa

ABSTRACT Fermentation-based chemical production strategies provide a feasible route for the rapid, safe, and sustainable production of a wide variety of important chemical products, ranging from fuels to pharmaceuticals. These strategies have yet to find wide industrial utilization due to their inability to economically compete with traditional extraction and chemical production methods. Here, we engineer for the first time the complex microbial biosynthesis of an anthocyanin plant natural product, starting from sugar. This was accomplished through the development of a synthetic, 4-strain Escherichia coli polyculture collectively expressing 15 exogenous or modified pathway enzymes from diverse plants and other microbes. This synthetic consortium-based approach enables the functional expression and connection of lengthy pathways while effectively managing the accompanying metabolic burden. The de novo production of specific anthocyanin molecules, such as calistephin, has been an elusive metabolic engineering target for over a decade. The utilization of our polyculture strategy affords milligram-per-liter production titers. This study also lays the groundwork for significant advances in strain and process design toward the development of cost-competitive biochemical production hosts through nontraditional methodologies. IMPORTANCE To efficiently express active extensive recombinant pathways with high flux in microbial hosts requires careful balance and allocation of metabolic resources such as ATP, reducing equivalents, and malonyl coenzyme A (malonyl-CoA), as well as various other pathway-dependent cofactors and precursors. To address this issue, we report the design, characterization, and implementation of the first synthetic 4-strain polyculture. Division of the overexpression of 15 enzymes and transcription factors over 4 independent strain modules allowed for the division of metabolic burden and for independent strain optimization for module-specific metabolite needs. This study represents the most complex synthetic consortia constructed to date for metabolic engineering applications and provides a new paradigm in metabolic engineering for the reconstitution of extensive metabolic pathways in nonnative hosts. IMPORTANCE To efficiently express active extensive recombinant pathways with high flux in microbial hosts requires careful balance and allocation of metabolic resources such as ATP, reducing equivalents, and malonyl coenzyme A (malonyl-CoA), as well as various other pathway-dependent cofactors and precursors. To address this issue, we report the design, characterization, and implementation of the first synthetic 4-strain polyculture. Division of the overexpression of 15 enzymes and transcription factors over 4 independent strain modules allowed for the division of metabolic burden and for independent strain optimization for module-specific metabolite needs. This study represents the most complex synthetic consortia constructed to date for metabolic engineering applications and provides a new paradigm in metabolic engineering for the reconstitution of extensive metabolic pathways in nonnative hosts.

Metabolic engineering of CHO cells to prepare glycoproteins

2018 ◽  
Vol 2 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Qiong Wang ◽  
Michael J. Betenbaugh
Keyword(s):  
Metabolic Engineering ◽  
Cho Cells ◽  
Genetic Manipulation ◽  
Chinese Hamster ◽  
Post Translational Modification ◽  
Effector Functions ◽  
Recombinant Glycoproteins ◽  
Production Platform ◽  
Chemical Inhibitors ◽  
Amino Acid Mutations

As a complex and common post-translational modification, N-linked glycosylation affects a recombinant glycoprotein's biological activity and efficacy. For example, the α1,6-fucosylation significantly affects antibody-dependent cellular cytotoxicity and α2,6-sialylation is critical for antibody anti-inflammatory activity. Terminal sialylation is important for a glycoprotein's circulatory half-life. Chinese hamster ovary (CHO) cells are currently the predominant recombinant protein production platform, and, in this review, the characteristics of CHO glycosylation are summarized. Moreover, recent and current metabolic engineering strategies for tailoring glycoprotein fucosylation and sialylation in CHO cells, intensely investigated in the past decades, are described. One approach for reducing α1,6-fucosylation is through inhibiting fucosyltransferase (FUT8) expression by knockdown and knockout methods. Another approach to modulate fucosylation is through inhibition of multiple genes in the fucosylation biosynthesis pathway or through chemical inhibitors. To modulate antibody sialylation of the fragment crystallizable region, expressions of sialyltransferase and galactotransferase individually or together with amino acid mutations can affect antibody glycoforms and further influence antibody effector functions. The inhibition of sialidase expression and chemical supplementations are also effective and complementary approaches to improve the sialylation levels on recombinant glycoproteins. The engineering of CHO cells or protein sequence to control glycoforms to produce more homogenous glycans is an emerging topic. For modulating the glycosylation metabolic pathways, the interplay of multiple glyco-gene knockouts and knockins and the combination of multiple approaches, including genetic manipulation, protein engineering and chemical supplementation, are detailed in order to achieve specific glycan profiles on recombinant glycoproteins for superior biological function and effectiveness.

Monetary policy and the effect of the transfer of oil prices to inflation

2020 ◽  
pp. 41-50
Author(s):  
Ph. S. Kartaev ◽  
I. D. Medvedev
Keyword(s):  
Monetary Policy ◽  
Inflation Targeting ◽  
Dynamic Models ◽  
Oil Prices ◽  
Oil Price ◽  
Oil Price Shocks ◽  
Negative Effects ◽  
Price Shocks ◽  
Policy Regime ◽  
The Impact

The paper examines the impact of oil price shocks on inflation, as well as the impact of the choice of the monetary policy regime on the strength of this influence. We used dynamic models on panel data for the countries of the world for the period from 2000 to 2017. It is shown that mainly the impact of changes in oil prices on inflation is carried out through the channel of exchange rate. The paper demonstrates the influence of the transition to inflation targeting on the nature of the relationship between oil price shocks and inflation. This effect is asymmetrical: during periods of rising oil prices, inflation targeting reduces the effect of the transfer of oil prices, limiting negative effects of shock. During periods of decline in oil prices, this monetary policy regime, in contrast, contributes to a stronger transfer, helping to reduce inflation.

Methods of parallel computing for multilevel fuzzy Takagi – Sugeno systems

2016 ◽  
pp. 141-149
Author(s):  
S.V. Yershov ◽  
◽  
R.М. Ponomarenko ◽  
Keyword(s):  
Dynamic Models ◽  
Fuzzy Inference ◽  
Knowledge Bases ◽  
Comparative Characteristic ◽  
Software Systems ◽  
Scientific Papers ◽  
Speed Up ◽  
Diagnostic Software ◽  
Takagi Sugeno

Parallel tiered and dynamic models of the fuzzy inference in expert-diagnostic software systems are considered, which knowledge bases are based on fuzzy rules. Tiered parallel and dynamic fuzzy inference procedures are developed that allow speed up of computations in the software system for evaluating the quality of scientific papers. Evaluations of the effectiveness of parallel tiered and dynamic schemes of computations are constructed with complex dependency graph between blocks of fuzzy Takagi – Sugeno rules. Comparative characteristic of the efficacy of parallel-stacked and dynamic models is carried out.

Dynamic Models of a Self-Excited Induction Generator Taking Iron Losses Into Account: a Comparative Study

2017 ◽  
Vol 10 (4) ◽  
pp. 239
Author(s):  
Rabah Rouas ◽  
Madjid Sibrahim ◽  
Salah Haddad ◽  
Nacereddine Benamrouche
Keyword(s):  
Comparative Study ◽  
Dynamic Models ◽  
Induction Generator ◽  
Iron Losses

A Comparison of Two Sub-structuring Techniques for Representing the Modal Properties of Tires

2001 ◽  
Vol 29 (1) ◽  
pp. 23-43 ◽  
Author(s):  
D. Tsihlas ◽  
T. Lacroix ◽  
B. Clayton
Keyword(s):  
Automobile Industry ◽  
Dynamic Models ◽  
Transfer Functions ◽  
Component Mode Synthesis ◽  
Numerical Techniques ◽  
The Past ◽  
Custom Made ◽  
Modal Behavior ◽  
Noise Vibration ◽  
Reduced Dynamic

Abstract Different numerical sub-structuring techniques for the representation of tire modal behavior have been developed in the past 20 years. By using these numerical techniques reduced dynamic models are obtained which can not only be used for internal studies but also be provided to the automobile industry and linked to reduced dynamic vehicle models in order to optimize the coupled vehicle-tire response for noise vibration and harshness purposes. Two techniques that have been developed in a custom-made finite element code are presented: 1) the component mode synthesis type models for which the wheel center interface is free and 2) the Craig and Bampton type models for which the wheel center interface is fixed. For both techniques the interface between the tire and the ground is fixed. The choice of fixed or free wheel center boundary condition is arbitrary. In this paper we will compare the formulation of these two numerical methods, and we will show the equivalency of both methods by showing the results obtained in terms of frequency and transfer functions. We will show that the two methods are equivalent in principle and the reduced dynamic models can be converted from one to the other. The advantages-disadvantages of each method will be discussed along with a comparison with experimentally obtained results.

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