Publications de Ljubisa Miskovic

Chattez avec Graph Search

Posez n’importe quelle question sur les cours, conférences, exercices, recherches, actualités, etc. de l’EPFL ou essayez les exemples de questions ci-dessous.

AVERTISSEMENT : Le chatbot Graph n'est pas programmé pour fournir des réponses explicites ou catégoriques à vos questions. Il transforme plutôt vos questions en demandes API qui sont distribuées aux différents services informatiques officiellement administrés par l'EPFL. Son but est uniquement de collecter et de recommander des références pertinentes à des contenus que vous pouvez explorer pour vous aider à répondre à vos questions.

Background: Pseudomonas putida is a promising candidate for the industrial production of biofuels and biochemicals because of its high tolerance to toxic compounds and its ability to grow on a wide variety of substrates. Engineering this organism for impro ...

Large-scale kinetic models are used for designing, predicting, and understanding the metabolic responses of living cells. Kinetic models are particularly attractive for the biosynthesis of target molecules in cells as they are typically better than other t ...

In an effort of overcoming the limited availability of fossil energy resources the focus of the research and development in the area of biofuels has moved towards developing the second generation of fuels that should be produced via microbial fermentation. The idea is to use as a feedstock inexpensive and abundant waste materials such as lignocellulosic biomass. The second generation biofuels should satisfy several criteria such as lower emission, higher energy density and should be less corrosive to engine

Accurate determination of physiological states of cellular metabolism requires detailed information about metabolic fluxes, metabolite concentrations and distribution of enzyme states. Integration of fluxomics and metabolomics data, and thermodynamics-base ...

Recent advancements in omics measurement technologies have led to an ever-increasing amount of available experimental data that necessitate systems-oriented methodologies for efficient and systematic integration of data into consistent large-scale kinetic ...

The engineering of the metabolism requires the building of reliable kinetic models of the metabolic pathways through the integration of the information from heterogeneous data sources. Unfortunately, the quantitative knowledge about fluxes, mechanisms or kinetic parameters of the constituent reactions of the metabolic network is most of the times uncertain or missing, due to limitations in the measurement techniques of the relevant biological properties of the cell and variability in experimental conditions

The limited supply of fossil fuels and environmental reasons shifted research in industry and academia towards finding their replacements. An important part of these efforts is focused on a sustainable production of the 2nd generation of biofuels. Among many proposed molecules, one of the most prominent fuel candidates is Methyl Ethyl Ketone (MEK). MEK, also referred in the literature as 2-butanone, is the most important commercially produced ketone with a broad application as a solvent for paints and adhes

Rational metabolic engineering methods are increasingly employed in designing the commercially viable processes for the production of chemicals relevant to pharmaceutical, biotechnology, and food and beverage industries. With the growing availability of omics data and of methodologies capable to integrate the available data into models, mathematical modeling and computational analysis are becoming important in designing recombinant cellular organisms and optimizing cell performance with respect to desired c

The production of second generation of biofuels by conversion of inexpensive feedstocks is a basis for future bio-sustainable economy. Among many proposed molecules, methyl ethyl ketone (MEK) emerged as one of the most prominent fuel candidates due to its high-energy density, low emissions, and good transport properties. There is no known natural producer of MEK, but there were some recent studies to express its production pathway in different organisms. In all of these attempts, reported yields were very l

Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmet ...

Kinetic models are essential for studying complex behavior and properties of metabolism. However, a persistent hurdle for constructing these models is uncertainty in the kinetic properties of enzymes. Currently available methods for building kinetic models cope in an indirect way with uncertainties by integrating data from different biological levels and origins into models. In this context, we have recently proposed iSCHRUNK1 a new approach for characterization and reduction of uncertainty that makes use o

Microbial cell factories are becoming a norm for commercially viable production of chemicals for pharmaceutical, biotechnology, food and beverage industries. However, engineering of microbial cell factories requires a simultaneous optimization of several criteria such as productivity, yield, titer, stress tolerance, all the while retaining the efficient, cost-effective and robust process. One of the most prominent examples where a rational metabolic engineering strategy played a key role is in the productio

Information about kinetics and enzyme activities while essential for quantitative understanding of metabolic dynamics remains rarely available and always involves uncertainty. In this work, we introduce the first computational methodology capable of determining the important enzymes in the network along with the operating ranges of their saturation by substrates and products and their parameters that correspond to a given metabolic flux and a given metabolite concentration. The proposed approach is based on

Mathematical modeling is an essential tool for a comprehensive understanding of cell metabolism and its interactions with the environmental and process conditions. Recent developments in the construction and analysis of stoichiometric models made it possib ...

The development of kinetic models is still facing the challenges such as large uncertainties in available data. Uncertainty originating from various sources including metabolite concentration levels, flux values, thermodynamic and kinetic data propagates to the kinetic parameter space and prevents an accurate identification of parameters. The uncertainty in parameters propagates further to the outputs of the corresponding kinetic models, such as control coefficients and time evolutions of metabolic fluxes a

Generating large omics datasets has become routine for gaining insights into cellular processes, yet deciphering these datasets to determine metabolic states remains challenging. Kinetic models can help integrate omics data by explicitly linking metabolite ...

Limited reserves of oil and natural gas and the establishment of new environmental policies sparked off intensive research towards sustainable production of the 2nd generation of biofuels, with Methyl Ethyl Ketone (MEK) being one promising fuel candidate. MEK is a commercially valuable petrochemical with an extensive application as a solvent. However, as of today, a sustainable and economically viable production of MEK has not yet been achieved despite several attempts of introducing biosynthetic pathways i

Engineering of microbial cell factories requires a simultaneous optimization of several criteria such as productivity, yield, titer, stress tolerance, all the while retaining the efficient, cost-effective and robust process. One of the most prominent examples where a rational metabolic engineering strategy played a key role is in the production of 1,4-butanediol (BDO) in E. coli. In this study, we used the ORACLE (Optimization and Risk Analysis of Complex Living Entities) framework to analyze the physiology

We have developed a consistently reduced core model for HeLa based on the genome scale human reconstruction. This reduced model includes the central carbon pathways, the electron transport chains, all the necessary transport and exchange reactions and the essential compartments for HeLa. In addition, the pyruvate/glutamate metabolism and the purine/pyrimidine catabolism for HeLa were incorporated based on available experimental observations. The core HeLa model consists of 273 reactions and 202 metabolites.

Ljubisa Miskovic

Chattez avec Graph Search

Identification of metabolic engineering targets for the enhancement of 1,4-butanediol production in recombinant E. coli using large-scale kinetic models

Large-scale kinetic metabolic models of Pseudomonas putida KT2440 for consistent design of metabolic engineering strategies

Kinetic models of metabolism that consider alternative steady-state solutions of intracellular fluxes and concentrations

Discovery and Evaluation of Novel Pathways for Production of the Second Generation of Biofuels

iSCHRUNK – In Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks

A Design-Build-Test cycle using modeling and experiments reveals interdependencies between upper glycolysis and xylose uptake in recombinant S. cerevisiae and improves predictive capabilities of large-scale kinetic models

Metabolic control analysis of the central carbon pathway in optimally grown E. coli

Discovery and evaluation of novel pathways for production of methyl ethyl ketone

Exploring enhancement of 1,4-butanediol production in recombinant E. coli using Large-scale kinetic models

Optimization of the production of methyl ethyl ketone in recombinant Pseudomonas putida using large-scale kinetic models

Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches

Identifying patterns in kinetic parameters that determine the impact of rate-limiting enzymes

Engineering improved productivity of 1,4-butanediol in E. coli – a kinetic modeling approach

iSCHRUNK – In Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks

Towards kinetic modeling of genome-scale metabolic networks without sacrificing stoichiometric, thermodynamic and physiology constraints

Deciphering ambiguous control over fluxes through characterization and reduction of uncertainty

Generative machine learning produces kinetic models that accurately characterize intracellular metabolic states

Exploring Biosynthetic Pathways for the Production of Five Methyl Ethyl Ketone Precursors

Exploring enhancement of 1,4-butanediol production in recombinant E. coli using large-scale kinetic models

Investigation of network flexibility and identification of reaction essentiality of human host cells infected by S. flexneri