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University of Groningen

Production routes toward podophyllotoxin

Seegers, Christina

DOI:

10.33612/diss.168957811

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.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2021

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Seegers, C. (2021). Production routes toward podophyllotoxin. University of Groningen. https://doi.org/10.33612/diss.168957811

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PRODUCTION ROUTES

toward

Podophyllotoxin

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The research described in this thesis was carried out in the Department of Chemical and Pharmaceutical Biology (Groningen Research Institute of Pharmacy, University of Groningen, the Netherlands) according to the requirements of the Graduate School of Science (Faculty of Science and Engineering, University of Groningen, the Netherlands).

This work was supported by European and regional funding. The PhytoSana project in the INTERREG IV A Deutschland-Nederland program: 34- INTERREG IV A I-1-01=193; and the Disposable Bioreactoren project in the Innovatief Actieprogramma Groningen: IAG3-D02.

Printing of this thesis was financially supported by the University Library and the Graduate School of Science, Faculty of Science and Engineering, University of Groningen, the Netherlands.

Cover design & illustrations: Ilse Schrauwers - isontwerp.nl Layout: Christel Seegers

Printed by: Gildeprint - www.gildeprint.nl ISBN: 978-94-92303-41-7

Copyright © 2021 by Christel Seegers. All rights reserved. No parts of this thesis may be reproduced or transmitted in any form or by any means without the prior permission in writing of the author.

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Production routes toward

podophyllotoxin

Proefschrift

ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen

op gezag van de

rector magnificus prof. dr. C. Wijmenga en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op vrijdag 28 mei 2021 om 12.45 uur

door

Christina Lamberta Catharina Seegers

geboren op 11 juni 1989 te Grubbenvorst

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Promotor Prof. dr. W.J. Quax Beoordelingscommissie Prof. dr. K. Taxis Prof. dr. J.T.M. Elzenga Prof. dr. S. Sukrasno

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5

Table of contents

Chapter 1 Introduction and scope of this thesis 7 Chapter 2 Toward metabolic engineering of podophyllotoxin

production

15

Chapter 3 Transcriptome analysis of Podophyllum hexandrum and functional expression of cytochrome P450 monooxygenases and NADPH-cytochrome P450 reductases in Escherichia coli

39

Chapter 4 Cytotoxic deoxypodophyllotoxin can be extracted in high purity from Anthriscus sylvestris roots by supercritical carbon dioxide

71

Chapter 5 Disposable bioreactor with integrated oxygen sensors for production of secondary metabolites in plant cell cultures

95

Chapter 6 Methyl jasmonate treatment increases podophyllotoxin production in Podophyllum hexandrum roots under glasshouse conditions

111

Chapter 7 Summary and future perspectives 133 Appendix Nederlandse samenvatting

List of abbreviations List of publications Curriculum Vitae Dankwoord

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Chapter X

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