University of Groningen
Metabolic engineering of Bacillus subtilis for terpenoids production Xue, Dan
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Publication date: 2018
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Xue, D. (2018). Metabolic engineering of Bacillus subtilis for terpenoids production. University of Groningen.
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appendix
Acknowledgments
List of publications
About the author
Acknowledgments
151
ACKNOWLEDGMENTS
The PhD journey is full of surprises and challenges, struggles and discovers. Finally, it has come to an end. I would have never finished this thesis and have this wonderful experience without help and support from the people who surrounded me all these years. Therefore, I would like to take the opportunity to express my sincere appreciate to everyone who provide me the possibility to complete this thesis.
Foremost, I would like to express my sincerest gratitude to my supervisor, Prof. Wim J.
Quax. Thank you for giving me the opportunity to join your research group even
though I came from a different scientific background than pharmaceutical biology. You opened up a totally new research area to me and supported me throughout my whole PhD period with patience, guidance, and immense knowledge. At many stages of my project, your valuable and constructive suggestions, positive outlook and confidence in my research inspired me and encouraged me to go further in scientific research. It is a real privilege and an honor for me to be your student and to share of your exceptional scientific knowledge.
I am thankful for the members of reading committee, Prof. Gert-Jan W. Euverink, Prof. Jan Maarten van Dijl and Prof. Colin. R. Harwood, for your kind willingness to read and assess this thesis.
Many thanks to Dr. Mark J. J. B. Sibbald who helped me to start this research project. Thank you for answering all my questions with great patience. Whenever I came up against difficulties on the experiments, you were always willing to help. Thank you for sharing your knowledge and experience on Bacillus subtilis.
Super special thanks to Rita, thank you so much for your continuous encouragements in my frustrating moments or when I lost my motivation. Not to mention many valuable advises and constantly help on my experiments as well as on my life. Thank you for being my paranymph, from the beginning to the end of my PhD period, you always stand by my side and support me. My dear friend Rita, thank you very much for everything.
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I would like to thank all my wonderful colleagues, current and former, in the 9th floor. Prof. Gerrit J. Poelarends, thank you for your valuable suggestions and comments regarding my research during the group meetings. Dr. Robbert H. Cool, when I faced problems about protein work, I know I could always get useful advices from you. Thank you for being so kind and for helping me with all of the protein work. More than that, I really enjoyed your funny songs in many defense parties. Dr. Ykelien L. Boersma, thank you for always willing to help and your kindness encourages. Ronald and Pieter, I sincerely appreciate all your help with the HPLC, GCMS and any other chemistry related questions. Thank you for helping me establish the analysis method and familiar with programs of these machines. I could not have finish my work without your help.
Putri, thank you for organizing the cinema and music nights, my life in Groningen
became more interesting because of you. Moreover, thank you for sharing your experience with me and encouraging me keep going on. You are such an amazing girl, I am so lucky to have a colleague and friend like you. Hegar and Ingy, we worked as a team, and shared protocols, data, experience of Bacillus subtilis and terpenoid. You are great colleagues and friends! Thank you for all those valuable scientific discussion and suggestions. Without your help I could not come to this point, I deeply appreciate your contributions to this thesis and your friendship. Jane, Yafeng, Yizhou, Brenda, Jielin,
Xinyu (金花们) thank you for the wonderful times we spent together. Jane, thank you for lending your bench to me and for lots of interesting talks. Yafeng, thank you for being my paranimph. Yizhou, thank you for your help on the qPCR experiment and for introducing the snails rice noodle to me. Brenda, thank you for sharing funny stories of being a new mammy. It has been a pleasure also meeting your little boy. Jielin, I will never forget the Xiaoling and Jiangkun joke. Thank you for all that happy time. Xinyu, thank you for giving the lovely name to our chat group. Our adorable 小金花, you always bring me lots of joy. Linda, Magda, Able, Jan, Joko, Haigen, Chao, Bin,
Guangcai, Lieuwe, Saravanan, Andreas, Zainal, Tjie, Saif, thank you for making a
cozy and friendly environment in the 9th floor. I wish all of you a lot of success and happiness in your PhD study. Many thanks to my former colleagues and friends in 9th floor: Magda, for helping me to grow my first batch of bacteria in the lab; Elena, for showing me how to perform my first PCR; Gudrun, for kindly giving me a very nice transformation protocol. My best wishes and thanks to: Pol, Carlos, Luis, Remco, Ilse,
Acknowledgments
153
Aart, Evelina, Ingrid, Mariana, Oktavia, Christel, Hans, Vinod, Harsh, Mehran, Yufeng, Ellen, Anna, Edzard, Jandre, Marianne, Bert-Jan, Jan Ytzen. Thank you
all for your friendship and help during my PhD study.
Many thanks to our secretaries, Yvonne and Janita, thank you for helping me with all these paper works and formalities.
I would like to thank Prof. Hao Zhang in Sichuan University, you are the one who lead me to the scientific world and encouraged me to pursue a further study abroad. Thank you so much for helping me to start my academic career and your constant support. Last but not the least, a million thanks to my dear family. 亲爱的爸爸、妈妈和源源，你 们不仅仅是我的家人，更是我最好的朋友。你们总是鼓励我追逐梦想并给我最坚定的支 持，谢谢你们一直以来无微不至的关怀，谢谢你们在我沮丧时给我力量，迷茫时给我方 向，能够成为你们的家人是我最大的幸运。
Now, it is the end of the thesis, and it is time to say goodbye to Groningen. I met a lot of wonderful and nice people in this city, who gave me support and helped me in different ways, thus, I would like to thank you all again for giving me the great memory in Groningen. I wish you all the best.
List of publications
155
LIST OF PUBLICATIONS
1. Dan Xue*, Hegar Pramastya*, Rita Setroikromo, Ingy I. Abdallah, Pieter G. Tepper, Wim J. Quax (* Authors contributed equally). High level production of amorphadiene using Bacillus subtilis as a terpenoid cell factory. Submitted
2. Ingy I Abdallah*, Dan Xue*, Hegar Pramastya, Ronald van Merkerk; Rita
Setroikromo; Wim J. Quax (* Authors contributed equally). Bacillus subtilis as an optimized cell factory for C30 terpenoid production. Submitted.
3. Guan Zheng, Dan Xue, Ingy I. Abdallah, Linda Dijkshoorn, Rita Setroikromo, Guiyuan Lv, Wim J. Quax. Metabolic Engineering of Bacillus subtilis for terpenoid production. 2015, Applied Microbiology and Biotechnology, 99:939-9406
4. Dan Xue, Ingy I. Abdallah, Ilse E. M. de Haan, et al. Enhanced C30 carotenoid production in Bacillus subtilis by systematic overexpression of MEP pathway genes. 2015, Applied Microbiology and Biotechnology, 99:5907-5915
5. Qin Huang, Hao Zhang, Dan Xue. Enhancement of antioxidant and hypolipidemic activity of Puerariae radix by fermentation with Aspergillus niger.
Submitted
6. Tiezhu Chen, Feiyan Wen, Yanli Fang, Yuxia Yang, Qingmao Fang, Hao Zhang,
Dan Xue. Effect of growth years on the plant, root system, yield and saponin
content. 2018, Jiangsu Agricultural Sciences, DOI ： 10.15889/j.issn.1002-1302.2018.10.032
7. Tiezhu Chen, Feiyan Wen, Tao Zhang, Dan Xue, Yanli Xia, Yuxia Zhang, Hao Zhang. A study of relationship between saponin of Paris polyphylla var.chinensis and ecological factor. 2018, Chinese Journal of Experimental Traditional Medical Formulae, 9:46-51
8. Qin Huang, Hao Zhang, Dan Xue. Enhancement of antioxidant activity of Radix Puerariae and red yeast rice by mixed fermentation with Monascus purpureus. 2017, Food Chemistry, 226: 89-94
9. Tiezhu Chen, Tao Zhang, Qingmao Fang, Feiyan Wen, Yuxia Yang, Hao Zhang,
Dan Xue. Potential distribution prediction and suitability evaluation of Paris
polyphylla var. chinensis based on Maxent modeling and GIS, 2017, Journal of
Chinese Medicinal Materials, 4: 803-806
Appendix
156
10. Tiezhu Chen, Feiyan Wen, Tao Zhang, Yuxia Yang, Qingmao Fang, Hao Zhang,
Dan Xue. Evaluation of saponins in Paris Polyphylla var. chinensis from
twenty-one growing areas. 2017, Chinese Traditional Patent Medicine, 11: 2345-2350 11. Kaiyuan Zhang, Wenxia Rao, Xianmei Yin, Hongxiang Yin, Dan Xue, Hao
Zhang. Two newly recorded varieties of Paris L. from Sichuan, China. 2016, Acta Botanica Boreali-Occidentalia Sinica, 11:2346-2348
12. Tiezhu Chen, Feiyan Wen, Tao Zhang, Yao Wang, Hao Zhang, Dan Xue. Research on the effects of rhizomes and seedling quality on growth, root system, yield and quality of Paris polyphylla chinensis Franch. 2016, Journal of Chinese Medicinal Materials, 39(12):2692-2696
13. Dan Lin, Yao Wang, Changyun Tang, Qin Huang, Hongxiang Yin, Dan Xue. Resources survey of the wild Paris in Qingchuan county of Sichuan province. 2016, West China Journal of Pharmaceutical Sciences, 31(02):181-184.
14. Peng Li, Dan Xue, Feiyan Wen, Yao Wang, Hongxiang Yin, Dan Lin, Changyun Tang, Hao Zhang. Additional morphological description of Paris forrestii (Takht) H. Li. and characteristic of its saponin compounds. 2016, Lishizhen Medicine and Materia Medica Research, 27(01):200-202.
15. Yao Wang, Dan Xue, Feiyan Wen, Hongxiang Yin, Dan Lin, Hao Zhang. Determination of five kinds of paris saponins in Paris fargesii by HPLC. 2015, West China Journal of Pharmaceutical Sciences, 30(4):469-470
16. Yashu Chen, Yao He, Chu Chen, Yi Zeng, Dan Xue, Feiyan Wen, Ling Wang, Hao Zhang, Junrong Du. Growth inhibition by pennogenyl saponins from Rhizoma paridis on hepatoma xenografts in nude mice. 2014, Steroids, 83:39-44. 17. Feiyan Wen, Hongxiang Yin, Chu Chen, Xianbo Liu, Dan Xue, Tiezhu Chen, Jun He, Hao Zhang. Chemical characteristics of saponins from Paris fargesii var.
brevipetala and cytotoxic activity of its main ingredient, paris saponin H. 2012,
Fitoterapia 83:627-635
18. Xianbo Liu, Hao Zhang, Zhengping Yong, Dan Xue. Isolation and identification of steroidal saponins of Paris polyphylla Smith var. pseudothibetica. 2010, West China Journal of Pharmaceutical Sciences, 25(5):508-511
List of publications
157 19. Dan Xue, Hongxiang Yin, Hao Zhang. Application of microscopy in
authentication and distinguishing of 11 Paris Species in western Sichuan. 2009, Microscopy Research and Technique, 72(10): 744-754.
20. Hongxiang Yin, Dan Xue, Nan Bai, Chu Chen, Yang Chen, Hao Zhang. Isolation and identification of major steroidal saponins of Paris Polyphylla. Smith var
stenophylla Franch. 2008, Journal of Sichuan University (Medical Science
Edition), 39(3): 485-488
21. Jie Li, Tao Yi, Hongshan Lai, Dan Xue, Hai Jiang, Huanchao Peng, Hao Zhang. Application of microscopy in authentication of traditional Tibetan medicinal plant
Halenia elliptica. 2008, Microscopy Research and Technique, 71(1):11-9
22. Hongxiang Yin, Dan Xue, Mei Wu, Yang Chen, Chu Chen, Hao Zhang. Quality estimation on material medica of rhizoma paridis from Sichuan & Yunnan province. 2007, Journal of Chinese Medicinal Materials, 30(7): 771-774
23. Hongxiang Yin, Hao Zhang, Dan Xue, Mei Wu, Linsen Qing, Chu Chen, Yang Chen. Quality evaluation of medicinal plant resources of Paris genus in Sichuan and Yunnan provinces. 2007, China Journal of Chinese Materia Medica. 32(13): 1344-1346
24. Hongxiang Yin, Hao Zhang, Dan Xue. Paris polyphylla var. emeiensis a new variety of Trilliaceae from Sichuan, China. 2007, Acta Phytotaxonomica Sinica, 45(6):822-827
25. Tao Yi, Hao Zhang, Jie Xie, Dan Xue. A new procedure for the preparative separation and isolation of Z-ligustilide from the roots of Angelica sinensis. 2007, Journal of Separation Science, 30(12):1973-1978
About the author
159
ABOUT THE AUTHOR
Dan Xue was born on the 12th of December 1984 in Henan, China. She grew up in Chengdu, where she finished her Bachelor in West China School of Pharmacy, Sichuan University in 2006. In the same year, she continued for a Master in Pharmacognosy in West China School of Pharmacy, Sichuan University. During her Master, she focused on purification, structure elucidation and biochemical characterization of bioactive compounds from Paris Polyphylla under supervision of Prof Hao Zhang. After obtaining her master degree, in October 2009, she moved to Groningen and started her PhD in the Department of Chemical and Pharmaceutical Biology in Groningen Research Institute of Pharmacy under the supervision of Prof. Wim J. Quax. She worked on the metabolic engineering of Bacillus subtilis for terpenoids production, the results of which are described in this thesis. In April 2014, she moved back to Chengdu and worked as a lecturer in the Department of Natural Products, West China School of Pharmacy, Sichuan University. Her research interests focus on bioactive chemical constituents, pharmacological activities, metabolic engineering and quality control of medicine plant.
