Investigations on ABC and MFS transporters of Streptomyces spp.

223 Pages·2015·10.55 MB·English

Investigations on

ABC and MFS transporters

of Streptomyces spp.

A dissertation presented to the
Faculty of Chemistry and Pharmacy of

Albert-Ludwigs University of Freiburg im Breisgau

for the degree of Doctor rerum naturalium

Submitted by
Irene Santillana Larraona
from Barcelona, Spain
- June 2015 -
Dean: Prof. Dr. Bernhard Breit
Chair of the doctoral committee: Prof. Dr. Stefan Weber
Referent: Prof. Dr. Andreas Bechthold
Co-referent: Jun. Prof. Dr. Stefan Günther
Third examiner: Prof. Dr. Oliver Einsle

Date of the examination: June 29, 2015
Date of promotion: July 2, 2015
I hereby declare that the presented work was completed independently by me and using
only the sources cited in the list of references.
Freiburg, June 2015.
| iii

____________________
Irene Santillana Larraona

Parts of this work have been published:
Presentation
“Inactivation of transporters by Redirect Technology”
PhD seminar. May 7, 2013.
Poster
Santillana, I.; Derochefort, J.; Zuo, C.; Bechthold, A.: “New insights into the rishirilide
gene cluster: Minimal PKS, oxygenases, hydrolases and transporters”. DPhG,
Annual meeting 2013. Drug discovery inspired by nature. Freiburg, October 09 – 11, 2013.
Santillana, I.; Yan, X.; Wunsch-Palasis, J.; Bechthold, A.: “Characterization of the
rishirilide transporters and their influence on its production”. Actinobacteria
within soils. Symposium. Münster, October 25 - 28, 2012.
Gessner, A.; Kroeger, J; Santillana, I.; Bechthold, A.: “Function, specificity and use of
transporters involved in biosynthesis of saccharide antibiotics or involved in the
efflux of antibiotics in Bacillus cereus”. Membrane proteins and biological
membranes. GRK 1478. Freiburg, January 10, 2012.
iv|
| v

This work was performed in the Institute of Pharmaceutical Biology and Biotechnology of
the University of Freiburg in the research group of

Prof. Dr. Andreas Bechthold,

who I want to sincerely thank for giving me this opportunity. Thank you for opening me the
doors of your working group and for supporting me during this time. Thank you for enabling
me to develop my own research and to work independently on a topic that I enjoyed.
vi|
I also want to thank:
 Jun. Prof. Dr. Stefan Günther for being my co-referent and for supporting me
especially during the first months of this work. I want to express my gratitude for
the welcome into the pharmaceutical bioinformatics working group.
| vii
 Prof. Dr. Oliver Einsle for so kindly accepting to be my third examiner.
 Dr. Gabriele Weitnauer for her help, organization and for the support with the
MolBio Bachelor Praktikum.
 The whole working group of pharmaceutical bioinformatics, and particularly
Dr. Anika Erxleben, Dr. Xavier Lucas, Stephan Flemming and Kersten Döring
for introducing me into the bioinformatics world and for the great start of my stay
in Freiburg. Thank you for enabling my participation in the StreptomeDB project.
 The former PhD students of the working group of Prof. Bechthold for all the initial
support. I want to give a big thank-you to Dr. Julia Wunsch-Palasis for showing
me everything necessary when I arrived to the lab and Dr. Theresa Siegl for her
help, advices and also fun in our office.
 The current working group for the good atmosphere and all cakes and Fanta we
enjoyed together. I want to especially thank Denise Deubel for her help and for
bringing her energy and good mood into the lab; Stefanie Hackl for all great
conversations about travelling and interesting life stories; Astrid Erber for taking
me into “uni-sports” and other cool activities; Yvonne Schmidt-Bohli for helping
me with protein related troubles and for being always available for a good advice;
and Suzan Samra for her huge humanity and for doing this working group a better
place.
 My “final phase” office colleagues Jasmin Kroeger and Tanja Heitzler for their
daily motivation words and because despite the hard days, we also had fun!
 Our TAs, Marcus Essing and Sandra Groß, for the computer and laboratory
support. Elisabeth Welle for her big and immediate help, for teaching me about
HPLC and for taking care of us and our lab.
 My “super” bachelor and diploma students Veronika Brinschwitz and Jannis
Brehm for their dedication, their help and their sense of humor. It was a pleasure
to share my project with you both.
 Dr. Tina Strobel and Stephan Flemming for all the time we enjoyed together, for
the relax evenings on the sofa, for the trips and the parties, because you made
possible that I never felt alone. Ihr seid so cool!
 Anja Greule for reading and correcting all this work. For being my “half of the
orange” in the lab, having fun and great scientific discussions. For sharing your
knowledge and for finding always time to help me and all the others. For being an
amazing colleague and even a better friend.
viii|
 Familie Löppenberg, für euer Interesse, eure Hilfe beim Schreiben während den
Wochenenden und für eure immer netten Worte.
 A Pablo y Ana por disfrutar juntos de mis visitas a Barcelona y por venir a conocer
Freiburg. A Mario, por ser la cosa más bonita, por sus enormes abrazos cuando llego
de visita y porque, aunque él no lo sepa, siempre me saca una sonrisa.
 A mis padres, por su amor y apoyo incondicional. Porque a pesar de la distancia,
siempre os siento conmigo y sois mi punto de referencia. Por recordarme cada día
que esta vida está para disfrutarla.
 Marius for all the effort and time dedicated to enhance this work. For being always
by my side and for taking me into your arms when everything felt “too much”. Thank
you for being a huge motivation to improve myself every day.
| ix

“Happiness only real when shared”
- Alexander Supertramp -
x|