Publications by Ljubisa Miskovic

Related publications (35)

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Keng Cher Soh, Stefano Andreozzi

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 om ...

Elsevier2016

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Milenko Tokic

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 ...

2020

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Meriç Ataman, Georgios Fengos, Tuure Eelis Hameri

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 ...

2019

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Stefano Andreozzi

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 ...

Academic Press Inc Elsevier Science2016

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Keng Cher Soh

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 ...

2017

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Aikaterini Zisaki

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 ...

Bentham Science Publishers2015

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Keng Cher Soh, Anirikh Chakrabarti

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 ...

2013

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

Vassily Hatzimanikatis, Ljubisa Miskovic, Subham Choudhury, Bharath Narayanan, David Michael Moret

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 ...

Springer Science and Business Media LLC2024

Discovery and Evaluation of Biosynthetic Pathways for the Production of Five Methyl Ethyl Ketone Precursors

Vassily Hatzimanikatis, Ljubisa Miskovic, Meriç Ataman, Noushin Hadadi, Milenko Tokic

The limited supply of fossil fuels and the establishment of new environmental policies shifted research in industry and academia towards sustainable production of the 2nd generation of biofuels, with Methyl Ethyl Ketone (MEK) being one promising fuel candi ...

2018

The Dawn of High-throughput and Genome-scale Kinetic Modeling: Recent Advances and Future Directions

Vassily Hatzimanikatis, Ljubisa Miskovic, Subham Choudhury, Ilias Toumpe

Researchers have invested much effort into developing kinetic models due to their ability to capture dynamic behaviors, transient states, and regulatory mechanisms of metabolism, providing a detailed and realistic representation of cellular processes. Hist ...

AMER CHEMICAL SOC2025

Quantification of uncertainty in metabolic networks through the sampling of kinetic data space

Vassily Hatzimanikatis, Ljubisa Miskovic

Study of a metabolic network with respect to the sensitivity of the metabolite concentrations and the metabolic fluxes to genetic, biochemical, and environmental variations requires knowledge of the kinetic properties of the enzymes in the network. Experim ...

2009

Data-driven controller tuning using the correlation approach

Ljubisa Miskovic

The essential ingredients of control design procedures include the acquisition of process knowledge and its efficient integration into the controller. In many practical control applications, a reliable mathematical description of the plant is difficult or ...

EPFL2006

Control Theory Concepts for Modeling Uncertainty in Enzyme Kinetics of Biochemical Networks

Vassily Hatzimanikatis, Ljubisa Miskovic, Georgios Savoglidis, Milenko Tokic

Analysis of the dynamic and steady-state properties of biochemical networks hinges on information about the parameters of enzyme kinetics. The lack of experimental data characterizing enzyme activities and kinetics along with the associated uncertainties i ...

2019

Enzyme annotation for orphan and novel reactions using knowledge of substrate reactive sites

Vassily Hatzimanikatis, Ljubisa Miskovic, Noushin Hadadi, Marianne Seijo

Thousands of biochemical reactions with characterized activities are “orphan,” meaning they cannot be assigned to a specific enzyme, leaving gaps in metabolic pathways. Novel reactions predicted by pathway-generation tools also lack associated sequences, l ...

National Academy of Sciences2019

Uncertainty reduction in biochemical kinetic models: Enforcing desired model properties

Vassily Hatzimanikatis, Ljubisa Miskovic, Michaël Roger Germain Moret

A persistent obstacle for constructing kinetic models of metabolism is uncertainty in the kinetic properties of enzymes. Currently, available methods for building kinetic models can cope indirectly with uncertainties by integrating data from different biol ...

2019

Modeling of uncertainties in biochemical reactions

Vassily Hatzimanikatis, Ljubisa Miskovic

Mathematical modeling is an indispensable tool for research and development in biotechnology and bioengineering. The formulation of kinetic models of biochemical networks depends on knowledge of the kinetic properties of the enzymes of the individual react ...

Wiley-Blackwell2010

Production of biofuels and biochemicals: in need of an ORACLE

Vassily Hatzimanikatis, Ljubisa Miskovic

The engineering of cells for the production of fuels and chemicals involves simultaneous optimization of multiple objectives, such as specific productivity, extended substrate range and improved tolerance – all under a great degree of uncertainty. The achi ...

Elsevier2010

Reconstructing Kinetic Models for Dynamical Studies of Metabolism using Generative Adversarial Networks

Vassily Hatzimanikatis, Ljubisa Miskovic, Subham Choudhury, Daniel Robert Weilandt, Pierre Guy Rémy Salvy, David Michael Moret

Kinetic models of metabolism relate metabolic fluxes, metabolite concentrations and enzyme levels through mechanistic relations, rendering them essential for understanding, predicting and optimizing the behaviour of living organisms. However, due to the la ...

NATURE PORTFOLIO2022

Supplementary datasets for the manuscript "Generative machine learning produces kinetic models that accurately characterize intracellular metabolic states" -Part 2

Vassily Hatzimanikatis, Ljubisa Miskovic, Subham Choudhury, Michaël Roger Germain Moret, Bharath Narayanan, David Michael Moret

Supplementary files containing datasets needed to reproduce the results of the manuscript "Generative machine learning produces kinetic models that accurately characterize intracellular metabolic states" by S. Choudhury et al. The code to use with these da ...

Zenodo2023

Constraint-based metabolic control analysis for rational strain engineering

Vassily Hatzimanikatis, Ljubisa Miskovic, Meriç Ataman, Tuure Eelis Hameri, Sofia Tsouka

The advancements in genome editing techniques over the past years have rekindled interest in rational metabolic engineering strategies. While Metabolic Control Analysis (MCA) is a well-established method for quantifying the effects of metabolic engineering ...

2021