University of Groningen
Terpenoid cell factory
Abdallah, Ingy Ibrahim Ahmed Fouad
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Publication date: 2018
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Abdallah, I. I. A. F. (2018). Terpenoid cell factory. Rijksuniversiteit Groningen.
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APPENDIX
Acknowledgements
List of Publications
Acknowledgements
261
Acknowledgments
At the end of the long and winding road to my PhD, the day I have been waiting for has finally arrived. Sometimes a PhD can be an exhausting and emotional struggle, however the support and care of people around me made that much easier. A lot of people embarked on this journey with me and contributed to it one way or another. Accordingly, its time to get hold of this precious moment to give thanks where it’s due. First and foremost, I am deeply grateful to my supervisor and promoter Prof. Wim J.
Quax. Wim, since our first SKYPE call, I felt that I will be comfortable in your lab and I
hoped you will be my supervisor. I admire your vast knowledge and understanding of different research areas. I learned a multitude of things from you, you opened my mind and helped me think about research in a deeper sense. Your guidance and support, during my ups and downs, is indeed, the reason I reached this point. I will not forget all the conferences and trips we went on together where you taught me not only about science but also life. I am fascinated by your knowledge about the history and culture of the places we visited, you made our trips such a memorable and enriching experience. Wim, thank you very much for giving me the chance to be your student and for making my whole PhD experience truly outstanding.
I would like to express my thankfulness to my second promoter Prof. Gerrit J.
Poelarends. Gerrit, I have always appreciated your passion for science, it is inspiring.
Whenever I needed help, you were always willing to give me a hand. Your input and remarks on my work were always valuable. Thank you for all the useful discussions and your guidance during important decisions phases.
My thanks also goes to the members of the assessment committee, Prof. Marco W.
Fraaije, Prof. Hidde J. Haisma and Prof. Volker F. Wendisch, for taking the time to
read and evaluate my thesis.
My heartfelt thanks to our amazing technicians, you are the pillars of the lab. Rita, you were the first person I met in Groningen. You picked me up at the train station when I first arrived, and made me feel welcomed. You are very kind and helpful inside and outside the lab. You did not hesitate to help me move and assemble my furniture. I would have been at a loss without your help. Not only that, you made sure I settled in the lab and lent me a hand with my experiments whenever I asked. I owe a lot to your good-natured and friendly attitude. Thank you for always being there during my PhD journey and for being my paranymph. Ronald, you are nothing but a true lifesaver. Whenever I came to you with a problem, you always found a solution. I appreciate all the discussions and experiment planning, without which I would have had much more hurdles in my work. I will not forget all the time we spent understanding software
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programs and optimizing experiments. You constantly helped me improve. You always gave me advice on my figures and my thesis layout. Your creative input during the cover design allowed it to turn out as fantastic as it is, I couldn't have done it without you. Added to that, thank you for writing the Dutch summary. Pieter, thank you for teaching me a lot about the GC-MS and for your patience whenever I forgot a detail about its operation. I can always count on you to work your magic on the machines. Special thank you to all my colleagues at the Department of Chemical and Pharmaceutical Biology for their assistance and the pleasant working environment. Thank you Prof. Frank J. Dekker, Prof. Hidde J. Haisma, Dr. Ykelien L. Boersma and Dr. Robbert H. Cool for the useful discussions and remarks during our group meetings. Ykelien, you were always willing to give me your advice when I needed, thanks a lot. My office mates: Dan, when I first arrived you were my one and only officemate. You helped me kickstart my work and introduced me to working with Bacillus subtilis. Shortly after, we were joined by Linda. Linda, your cheerful outgoing attitude perked up the office. Your research input was always helpful. I won’t forget our trip to Switzerland where I experienced snow and skiing for the first time, Dan, I made you take tons of pictures of me, please forgive me, they were all wonderful. Which brings me to Jane and Yafeng. Thanks to you I got to experience the Chinese essence as if I visited China without leaving my desk. I took pleasure in hearing your Chinese conversations and talking about Chinese culture. I also have to remember the rest of the girls, Magda, Putri, Yizhou, Brenda, Christel and Jielin. I enjoyed our girls’ nights, the food, movies and games. You brightened my days. Magda, thank you for being my paranymph. To the men of the 9th floor, Hegar, Jan, Joko, Abel, Chao,
Lieuwe, Zainal, Haigen, Tjie, Saif, Saravanan and Andreas, thank you for being good
colleagues and offering your assistance. Not to forget the people on the 3rd floor:
Hannah and Martijn, I enjoyed our time in the PhFun committee. Also, Thea, Olivia, Laura, Petra, Roberta, Bin and Hao, thank you. To the colleagues I only met recently, Eleonora, Guangcai, Xinyu, Zhanping, Ali, Marie, Fangyuen and Siwei, good luck
with your research in this amazing group. Finally, my thanks to the previous members of the department, Yufeng, Ingrid, Mehran, Harsh, Hans, Bert-Jan, Edzard and Jan
Ytzen. We didn't spend a lot of time together, however I enjoyed our lunches and
seminars.
I supervised some excellent students during my PhD. I would especially like to acknowledge, Esmée and Pretty, for their hard work and dedication. I wish you success in your future studies and work.
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I can’t overlook our super secretaries, Janita and Yvonne, thank you for always taking care of my paper work and helping me with all the formal procedures. I would also like to thank Cathy for her assistance and kindness.
To my Egyptian friends in Groningen, you were my home away from home. My comrade in arms, Rana, your presence was a great comfort for me. I enjoyed walking around the city center, shopping and eating with you. I won’t forget the memories we made on our crazy trips spanning Europe. You left a gap in my life after your departure. I wish we can stay close friends no matter how far we are. Eman and Sabry, I could always depend on you. I knew I can count on you to have my back whenever the need emerged. You were always willing to help. Thank you for being there. Marwa,
Samer, Mohamed and Ahmed Younis, although we didn’t meet often, but the times
we gathered and shared an Egyptian meal gave me a sense of home. Samer, without you I probably would have spent some time sleeping on the floor, thank you for assembling my IKEA bed. Finally, Asmaa and Ahmed Soliman, meeting you in Groningen was a very nice coincidence. I enjoyed spending time with you. Maryame, I only got to know you recently but that little amount of time was delightful.
I owe a lot of gratitude to my Professors at the Faculty of Pharmacy, Alexandria University. Without your guidance, I wouldn’t be here today. To my professors in the Department of Pharmacognosy, thank you for your advice and encouragement. To my fellow colleagues in the department, thank you for your constant support, you push me to strive.
I would never forget my friends back home, your constant messages and phone calls are what kept me going during the hard times. Ingy, Maha, Eman, Ragia, Hanzadha,
Ghada, May and Nevine, I am truly blessed for having you as my friends for a lifetime.
Last but foremost, I would like to express my deepest gratitude to my family. You are my light in the darkness, my strength and my refuge. You are the best part of me. All that I am, I owe to you. Mommy, thank you for letting me grow my own wings and fly in spite of all the worries it brought to you. You are always by my side to catch me when I fall and to praise me when I succeed. Most importantly, you love me unconditionally. No words can express how important you are to me. Thank you for being the best mom ever, I couldn’t wish for a better mom. Pappy, thank you for your endless support, all your sacrifices, for believing in me since day one, and letting me be me. You make me feel safe and love me beyond anything. You know what I am thinking of before I even do and you push me to follow my dreams. You are my hero. Thank you for being the dad you are. Ola, you are my sister, my best friend, my mirror, my other half and my confidante. You understand all my quirks and insecurities. You
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know me better than anyone. I can’t imagine life without you. Thank you for all the dreams, the laughter and the tears. Thank you for all that you are and all that you do.
Ezz El Din, my cute nephew, I hope you will read this when you grow up. You are a
precious bundle of joy that brightens our life. Whenever I felt down, I would watch home videos of you or video call you just to see you saying you love me. When you smile and say you miss me, I am over the moon. Mahmoud, thank you for being the brother I didn’t have. My auntie Moshira, you are not only my second mother but also my sister and true friend. I admire how tough you are in the face of adversity. You inspire me to be fearless in pursuit of my dreams and to strive to be the best I can be. I am blessed to have you in my life. Raneem, we grew up together and I consider you my second sister. No matter how serious life gets, I can be as silly and crazy as I want with you. You are my partner in crime. Thank you for being an awesome cousin. I love you all so much. Finally, I thank all my family members whom I didn't mention, not that they didn't have a role in my success, but that I can't give them enough appreciation.
Ingy
.March 2018 Groningen
List of Publications
267
List of publications
1. Hammoda, H.M., Ghazy, N.M., Harraz, F.M., Radwan, M.M., ElSohly, M.A.,
Abdallah, I.I. (2013). Chemical constituents from Tribulus terrestris and screening
of their antioxidant activity. Phytochemistry 92, 153-159.
2. Harraz, F.M., Ghazy, N.M., Hammoda, H.M., Nafeaa, A.A., Abdallah, I.I. (2015). Hepatoprotective and antioxidant activities of Tribulus terrestris. Journal of Physiology and Pharmacology Advances 5(11), 787-794.
3. Xue, D., Abdallah, I.I., de Haan, I.E.M., Sibbald, M.J.J.B., Quax, W.J. (2015). Enhanced C30 carotenoid production in Bacillus subtilis by systematic
overexpression of MEP pathway genes. Applied Microbiology and Biotechnology 99(14), 5907-5915.
4. Guan, Z.#, Xue, D.#, Abdallah, I.I., Dijkshoorn, L., Setroikromo, R., Lv, G., Quax,
W.J. (2015). Metabolic engineering of Bacillus subtilis for terpenoid production. Applied Microbiology and Biotechnology 99(22), 9395-9406.
5. Abdallah, I.I.#, Czepnik, M.#, van Merkerk, R., Quax, W.J. (2016). Insights into the
three-dimensional structure of amorpha-4,11-diene synthase and probing of plasticity residues. Journal of Natural Products 79(10), 2455–2463.
6. Abdallah, I.I., Quax, W.J. (2017). A Glimpse into the biosynthesis of terpenoids. KnE Life Sciences, 81-98.
7. Abdallah, I.I., Quax, W.J. (2018). Insights into the structure-function relations of amorpha-4,11- diene synthase. Biotarget 2.
8. Abdallah, I.I.#, Xue, D.#, Pramastya, H., van Merkerk, R., Setroikromo, R., Quax,
W.J., Bacillus subtilis as an optimized cell factory for C30 terpenoid production.
Manuscript submitted.
9. Abdallah, I.I.#, Pramastya, H.#, van Merkerk, R., Sukrasno, Quax, W.J., Metabolic
engineering of Bacillus subtilis towards taxadiene biosynthesis as the first committed step for Taxol production. Manuscript submitted.
List of Publications
268
10. Abdallah, I.I., van Merkerk, R., Klumpenaar, E., Quax, W.J., Catalysis of amorpha-4,11-diene synthase unraveled and improved by mutability landscape guided engineering. Manuscript submitted.
11. Abdallah, I.I., van Merkerk, R. & Quax, W.J., Insights into the promiscuity of amorpha-4,11-diene synthase obtained from mutability landscape engineering. Manuscript to be submitted.
12. Pramastya, H.#, Xue, D.#, Setroikromo, R., Abdallah, I.I., Tepper, P.G., Quax, W.J.,
High level production of amorphadiene using Bacillus subtilis as terpenoid cell factory. Manuscript in preparation.
About the author
269
About the author
Ingy was born on the 12th of February 1987 in Alexandria, Egypt.
She grew up in Alexandria where she completed her secondary education. In June 2008, she finished her BSc in Pharmaceutical Sciences at Faculty of Pharmacy, Alexandria University in Egypt and graduated with distinction honour. She was ranked 3rd on her
class and was offered a job as an assistant lecturer. She started teaching undergraduate Pharmacy students while pursuing a research master on Pharmacognosy and Natural Product
Chemistry under the supervision of Prof. Nabila M. Ghazy, Prof. Fathalla M. Harraz and Prof. Hala M. Hammoda. Her master thesis was entitled “Phytochemical study of Tribulus terrestris”. She obtained her MSc degree from Faculty of Pharmacy, Alexandria University on September 2012. She searched for an opportunity to pursue her doctoral degree abroad and was successfully awarded an Erasmus Mundus, Fatima Al Fihri scholarship to the University of Groningen. In August 2013, she moved to Groningen to start her PhD in the Department of Chemical and Pharmaceutical Biology in Groningen Research Institute of Pharmacy (GRIP) under the supervision of Prof. Wim J. Quax and Prof. Gerrit J. Poelarends. Her research focused on creating a microbial cell factory for terpenoid production and in turn studying the enzymes involved in this process especially terpene synthases such as amorpha-4,11-diene synthase, of which the results are described in this thesis. Ingy is passionate about research and teaching. She enjoys presenting her research in conferences. In Egypt, she played handball professionally and got to experience playing the game in Groningen during her first year. In her free time, she likes reading novels.