High titer mevalonate fermentation and its feeding as a building block for isoprenoids (isoprene and sabinene) production in engineered Escherichia coli |
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| Affiliation: | 1. CAS Key Laboratory of Bio-based Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, China;2. College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China;3. Faculty of Agriculture, Mansoura University, Mansoura 35516, Egypt;4. School of Life Science, Jilin University, Changchun, China;1. Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China;2. State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, PR China;3. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, PR China;4. Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072, PR China;1. Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Republic of Korea;2. Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, Republic of Korea;3. Department of Korean Medicine, Semyung University, Jecheon, Chungbuk 27136, Republic of Korea;1. Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA;2. Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;3. Department of Bioengineering, University of California, Berkeley, CA 94720, USA;4. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA;5. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Denmark;1. Bio-based Chemistry Research Center, Advanced Convergent Chemistry Division, Korea Research Institute of Chemical Technology, P.O. Box 107, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114 Republic of Korea;2. Division of Chemical Engineering and Materials Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea;3. Department of Biological and Chemical Engineering, Hongik University, 2639 Sejong-ro, Sinan-ri, Jochiwon-eup, Sejong-si 30016, Republic of Korea;4. Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea;5. Metabolic Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus program), KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea;6. Department of Chemical and Biomolecular Engineering (BK21 Plus program), KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea |
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| Abstract: | Isoprenoids are important fine chemicals as material monomers, advanced fuels and pharmaceuticals. A variety of natural isoprenoids can be synthesized by engineered microbial strains. This work established a process by dividing the current isoprenoid pathway into the upstream fermentation process, from sugar to mevalonate (MVA), and the downstream process, from MVA to the target isoprenoids. The results showed that significant differences existed in the process conditions between the upstream and downstream fermentations. After individually optimizing the process conditions, the upstream MVA production (84.0 g/L, 34.0% and 1.8 g/ L/h) and downstream isoprene production (11.0 g/L and 0.23 g/L/h) were greatly improved in this two-step process. Flask fermentation experiments also confirmed that two-step route can significantly improve the sabinene titer to 150 mg/L (6.5-fold of the sabinene titer in an earlier flask study of our lab). Therefore, the two-step route proposed in this study may have potential benefits towards the current isoprenoids production directly from glucose. The high titer and yield of MVA indicate that MVA has great potential to be more broadly utilized as starting precursor in synthetic biology. |
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| Keywords: | Mevalonate Isoprene Sabinene Betaine Biosynthesis |
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