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University of Groningen Thermodynamic and stoichiometric constraint-based inference of metabolic phenotypes Leupold, Karl Ernst Simeon

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University of Groningen

Thermodynamic and stoichiometric constraint-based inference of metabolic phenotypes

Leupold, Karl Ernst Simeon

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

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Publication date: 2018

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Leupold, K. E. S. (2018). Thermodynamic and stoichiometric constraint-based inference of metabolic phenotypes. University of Groningen.

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Thermodynamic and stoichiometric

constraint-based inference of

metabolic phenotypes

Karl Ernst Simeon Leupold

2018

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The work published in this thesis was carried out in the research group Molecular Systems Biology of the Groningen Biomolecular Science and Biotechnology Institute (GBB) of the University of Groningen, The Netherlands. The research was financially supported by the BE-BASIC consortium.

ISBN: 978-94-034-1035-7 (printed version) ISBN: 978-94-034-1034-0 (electronic version)

Copyright © 2018 Karl Ernst Simeon Leupold

All rights reserved. No part of this publication may be produced, stored in a retrieval system of any nature, or transmitted in any form or by any means, elec-tronic, mechanical, including photocopying and recording, without prior written permission of the author.

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Thermodynamic and stoichiometric

constraint-based inference of

metabolic phenotypes

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. E. Sterken

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Tuesday 18 September 2018 at 09.00 hours

by

Karl Ernst Simeon Leupold

born on 17 March 1987 in Berlin, Germany

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Supervisors

Prof. M. Heinemann Prof. A.J.M. Driessen

Assessment Committee

Prof. B. Jayawardhana Prof. B.M. Bakker Prof. F. Bruggeman

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Table of Contents

5

Table of Contents

Chapter 1 Introduction and aim of this thesis 7

Chapter 2 An upper limit in Gibbs energy dissipation governs cellular metabolism 19 Chapter 3 thermodynamic-based tool for flux predictions in Implementation and application of a new

genome-scale metabolic models 71 Chapter 4 Saccharomyces cerevisiae goes through distinct metabolic phases during its replicative lifespan 97 Chapter 5 On the mechanistic reasons behind the observed limit in Gibbs energy dissipation of

cellular metabolism 129

Chapter 6 Conclusion and future perspective 143

Nederlandse samenvatting 146

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