Publications de Ljubisa Miskovic

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

Ljubisa Miskovic, Vassily Hatzimanikatis

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

Dataset - Kinetic-model-guided engineering of multiple S. cerevisiae strains improves p-coumaric acid production

Ljubisa Miskovic, Vassily Hatzimanikatis, Francisco Javier Perez Saez, Maria Masid Barcon, Wei Jiang

Dataset supporting the results presented in the paper entitled "Kinetic-model-guided engineering of multiple S. cerevisiae strains improves p-coumaric acid production" by Narayanan, Jiang & Wang et al (https://doi.org/10.1016/j.ymben.2025.06.008). Dataset ...

Zenodo2025

Dataset - Generative Approaches to Kinetic Parameter Inference in Metabolic Networks via Latent Space Exploration

Ljubisa Miskovic, Vassily Hatzimanikatis

Dataset needed to reproduce the results in the manuscript by "Generative Approaches to Kinetic Parameter Inference in Metabolic Networks via Latent Space Exploration" by S. Choudhury et al. (under review, a preprint available at https://www.biorxiv.org/con ...

Zenodo2025

Rational strain design with minimal phenotype perturbation

Ljubisa Miskovic, Vassily Hatzimanikatis, Daniel Robert Weilandt

Devising genetic interventions for desired cellular phenotypes remains challenging regarding time and resources. Kinetic models can accelerate this task by simulating metabolic responses to genetic perturbations. However, exhaustive design evaluations with ...

Nature Portfolio2024

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

Ljubisa Miskovic, Vassily Hatzimanikatis

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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, Michaël Roger Germain 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

Supplementary datasets for the manuscript "Generative machine learning produces kinetic models that accurately characterize intracellular metabolic states" - Part 3

Ljubisa Miskovic, Vassily Hatzimanikatis, Michaël Roger Germain 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 (https://doi.org/10.1101/2023. ...

Zenodo2023

Supplementary dataset for Enzyme promiscuous profiles for protein sequence and reaction annotation

Ljubisa Miskovic, Vassily Hatzimanikatis, Homa Mohammadi Peyhani, Anastasia Sveshnikova

The data and scripts used to produce, analyze, and visualize the results of the manuscript Enzyme promiscuous profiles for protein sequence and reaction annotation by Homa MohammadiPeyhani, Anastasia Sveshnikova, Ljubisa Miskovic, and Vassily Hatzimanikati ...

Zenodo2023

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

Ljubisa Miskovic, Vassily Hatzimanikatis, Pierre Guy Rémy Salvy, Daniel Robert Weilandt

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

A genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics

Ljubisa Miskovic, Vassily Hatzimanikatis, Pierre Guy Rémy Salvy, Maria Masid Barcon, Mohammadomid Oftadeh

Eukaryotic organisms play an important role in industrial biotechnology, from the production of fuels and commodity chemicals to therapeutic proteins. To optimize these industrial systems, a mathematical approach can be used to integrate the description of ...

Nature Portfolio2021

Constraint-based metabolic control analysis for rational strain engineering

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

Uncertainty reduction in biochemical kinetic models: Enforcing desired model properties

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

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

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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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

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

Ljubisa Miskovic, Vassily Hatzimanikatis, 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