University of Groningen
Improving Bacillus subtilis as a cell factory for heterologous protein production by adjusting
global regulatory networks
Cao, Haojie
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Publication date: 2018
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Cao, H. (2018). Improving Bacillus subtilis as a cell factory for heterologous protein production by adjusting global regulatory networks. University of Groningen.
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Improving Bacillus subtilis
as a cell factory
for heterologous
protein production
by adjusting
global regulatory networks
The work described in this thesis was carried out in Molecular Genetics Group of the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) of the University of Groningen, the Netherlands. The candidate was fi nancially supported by the China Scholarship Council (CSC).
Printing of this thesis was fi nancially supported by the Graduate School of Sci-ence and Engineering and the University of Groningen.
Cover design & layout: Lovebird design
www.lovebird-design.com Printed: Eikon+
ISBN: 978-94-034-0788-3 978-94-034-0787-6 (ebook) © 2018. Haojie Cao, Groningen, the Netherlands.
All rights reserved.
Improving Bacillus subtilis as a cell
factory for heterologous protein
production by adjusting global
regulatory networks
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnifi cus Prof. E. Sterken
and in accordance with
the decision by the College of Deans.
This thesis will be defended in public on
Monday 9 July 2018 at 9:00 hours
by
Haojie Cao
born on 16 March 1987
in Henan, China
The work described in this thesis was carried out in Molecular Genetics Group of the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) of the University of Groningen, the Netherlands. The candidate was fi nancially supported by the China Scholarship Council (CSC).
Printing of this thesis was fi nancially supported by the Graduate School of Sci-ence and Engineering and the University of Groningen.
Cover design & layout: Lovebird design
www.lovebird-design.com Printed: Eikon+
ISBN: 978-94-034-0788-3 978-94-034-0787-6 (ebook) © 2018. Haojie Cao, Groningen, the Netherlands.
All rights reserved.
Improving Bacillus subtilis as a cell
factory for heterologous protein
production by adjusting global
regulatory networks
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnifi cus Prof. E. Sterken
and in accordance with
the decision by the College of Deans.
This thesis will be defended in public on
Monday 9 July 2018 at 9:00 hours
by
Haojie Cao
born on 16 March 1987
in Henan, China
Supervisor
Prof. dr. O.P. Kuipers
Co-supervisor
Prof. dr. J.W. Veening
Assessment Committee
Prof. J.M. van Dijl
Prof. W.J. Quax
Prof. A.T. Kovacs
CONTENTS
Chapter 1
General Introduction 7
Chapter 2
Cell surface engineering of Bacillus subtilis improves pro-duction yields of heterologously expressed α-amylases 35
Chapter 3
Boosting heterologous protein production yield by adjust-ing global nitrogen and carbon metabolic regulatory net-works in Bacillus subtilis 61
Chapter 4
Stronger repression of carbon metabolic pathways and de-repression of nitrogen metabolic benefi t heterologous protein synthesis in Bacillus subtilis 91
Chapter 5
Infl uence of global gene regulatory networks on single cell heterogeneity of green fl uorescent protein production in Bacillus subtilis 121
Chapter 6
General Discussion 145 Nederlandse samenvatting 159 中文总结 165 Acknowledgments 169Supervisor
Prof. dr. O.P. Kuipers
Co-supervisor
Prof. dr. J.W. Veening
Assessment Committee
Prof. J.M. van Dijl
Prof. W.J. Quax
Prof. A.T. Kovacs
CONTENTS
Chapter 1
General Introduction 7
Chapter 2
Cell surface engineering of Bacillus subtilis improves pro-duction yields of heterologously expressed α-amylases 35
Chapter 3
Boosting heterologous protein production yield by adjust-ing global nitrogen and carbon metabolic regulatory net-works in Bacillus subtilis 61
Chapter 4
Stronger repression of carbon metabolic pathways and de-repression of nitrogen metabolic benefi t heterologous protein synthesis in Bacillus subtilis 91
Chapter 5
Infl uence of global gene regulatory networks on single cell heterogeneity of green fl uorescent protein production in Bacillus subtilis 121
