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University of Groningen Adding tools to the box: facilitating host strain engineering of Penicillium chrysogenum for the production of heterologous secondary metabolites Pohl, Carsten

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University of Groningen

Adding tools to the box: facilitating host strain engineering of Penicillium chrysogenum for the

production of heterologous secondary metabolites

Pohl, Carsten

DOI:

10.33612/diss.119054818

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: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Pohl, C. (2020). Adding tools to the box: facilitating host strain engineering of Penicillium chrysogenum for the production of heterologous secondary metabolites. University of Groningen.

https://doi.org/10.33612/diss.119054818

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Adding tools to the box:

facilitating host strain engineering of

Penicillium chrysogenum for

the production of

heterologous secondary metabolites

(3)

The work described in this thesis was carried out in the Molecular Microbiology Group of the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) of the University of Groningen, The Netherlands. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/under REA grant agreement no. [607332].

Author: Carsten Pohl

Cover: Paula Spikermann

Layout & printing: Off Page – Amsterdam, www.offpage.nl

ISBN: 978-3-00-064764-2

The work described in this thesis was carried out in the Molecular Microbiology  Group  of  the  Groningen  Biomolecular  Sciences  and  Biotechnology  Institute  (GBB) of the University of Groningen, The Netherlands. The research leading to  these  results  has  received  funding  from  the  People  Programme  (Marie  Curie  Actions)  of  the  European  Union’s  Seventh  Framework  Programme  FP7/2007‐ 2013/under REA grant agreement no. [607332].                   Author:        Carsten Pohl  Cover:        Paula Spikermann‐Freidank   Layouting:         Michael xxx, Off Page  Printed by         Off Page – Amsterdam, www.offpage.nl  ISBN          Please request an ISBN for me                 

 

 

Adding tools to the box: facilitating 

host strain engineering 

of Penicillium chrysogenum for the production of 

heterologous secondary metabolites

 

 

PhD thesis 

  to obtain the degree of PhD at the   University of Groningen   on the authority of the   Rector Magnificus Prof. C. Wijmenga   and in accordance with   the decision by the College of Deans     This thesis will be defended in public on   Monday 2 March 2020 at 11.00 hours    by 

 

Carsten Pohl 

born on 13 November 1987  in Potsdam, Germany 

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Adding tools to the box:

facilitating host strain engineering of

Penicillium chrysogenum for

the production of

heterologous secondary metabolites

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans This thesis will be defended in public on

Monday 2 March 2020 at 11.00 hours

by

Carsten Pohl born on 13 November 1987

in Potsdam, Germany

The work described in this thesis was carried out in the Molecular Microbiology  Group  of  the  Groningen  Biomolecular  Sciences  and  Biotechnology  Institute  (GBB) of the University of Groningen, The Netherlands. The research leading to  these  results  has  received  funding  from  the  People  Programme  (Marie  Curie  Actions)  of  the  European  Union’s  Seventh  Framework  Programme  FP7/2007‐ 2013/under REA grant agreement no. [607332].                   Author:        Carsten Pohl  Cover:        Paula Spikermann‐Freidank   Layouting:         Michael xxx, Off Page  Printed by         Off Page – Amsterdam, www.offpage.nl  ISBN          Please request an ISBN for me                 

 

 

Adding tools to the box: facilitating 

host strain engineering 

of Penicillium chrysogenum for the production of 

heterologous secondary metabolites

 

 

PhD thesis 

  to obtain the degree of PhD at the   University of Groningen   on the authority of the   Rector Magnificus Prof. C. Wijmenga   and in accordance with   the decision by the College of Deans     This thesis will be defended in public on   Monday 2 March 2020 at 11.00 hours    by 

 

Carsten Pohl 

born on 13 November 1987  in Potsdam, Germany 

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Promotors

Prof. A. J. M. Driessen Prof. R. A. L. Bovenberg

Assessment committee

Prof. R. de Vries

Prof. I. J. van der Klei Prof. M. W. Fraaije

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Table of Contents

Chapter 1 Genome editing and metabolic engineering of 7

filamentous fungi for biosynthesis of natural products

Chapter 2 CRISPR/Cas9 based genome editing of 33

Penicillium chrysogenum

Chapter 3 Identification of the decumbenone biosynthetic gene 67

cluster in Penicillium decumbens and the importance for production of calbistrin

Chapter 4 A Penicillium chrysogenum platform strain for 111

secondary metabolite production

Chapter 5 Three more tools in the box for genetic engineering of 153

Penicillium chrysogenum – rapid prototyping of

genomic integrated expression cassettes, an aldehyde-inducible promoter and degron-tags for faster protein degradation

Chapter 6 Summary 181

Chapter 7 Acknowledgements 193

Curriculum vitae 198

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