Metabolic engineering of Corynebacterium glutamicum for the production of 3-hydroxypropionic acid from glucose and xylose |
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| Institution: | 1. Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;2. Tsinghua Innovation Center in Dongguan, Dongguan 523808, China;1. Clean Energy Research Center, Korea Institute of Science and Technology, Hwarang-ro 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea;2. Department of Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea;3. Department of Food Science and Biotechnology, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea;1. Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan;2. Research Center, Asahi Glass Co., Ltd., 1150 Hazawacho, Yokohama 221-8755, Japan;1. Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Republic of Korea;2. Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-742, Republic of Korea;3. Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea;1. Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea;2. Department of Food Science and Development, Kyungil University, Gyeongsan 38428, Republic of Korea;3. Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang 25354, Republic of Korea;4. Institutes of Green Bio Science and Technology, Seoul National University, Pyeongchang 25354, Republic of Korea;1. CAS Key Lab of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China |
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| Abstract: | 3-Hydroxypropionic acid (3-HP) is a promising platform chemical which can be used for the production of various value-added chemicals. In this study,Corynebacterium glutamicum was metabolically engineered to efficiently produce 3-HP from glucose and xylose via the glycerol pathway. A functional 3-HP synthesis pathway was engineered through a combination of genes involved in glycerol synthesis (fusion of gpd and gpp from Saccharomyces cerevisiae) and 3-HP production (pduCDEGH from Klebsiella pneumoniae and aldehyde dehydrogenases from various resources). High 3-HP yield was achieved by screening of active aldehyde dehydrogenases and by minimizing byproduct synthesis (gapAA1GΔldhAΔpta-ackAΔpoxBΔglpK). Substitution of phosphoenolpyruvate-dependent glucose uptake system (PTS) by inositol permeases (iolT1) and glucokinase (glk) further increased 3-HP production to 38.6 g/L, with the yield of 0.48 g/g glucose. To broaden its substrate spectrum, the engineered strain was modified to incorporate the pentose transport gene araE and xylose catabolic gene xylAB, allowing for the simultaneous utilization of glucose and xylose. Combination of these genetic manipulations resulted in an engineered C. glutamicum strain capable of producing 62.6 g/L 3-HP at a yield of 0.51 g/g glucose in fed-batch fermentation. To the best of our knowledge, this is the highest titer and yield of 3-HP from sugar. This is also the first report for the production of 3-HP from xylose, opening the way toward 3-HP production from abundant lignocellulosic feedstocks. |
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| Keywords: | 3-Hydroxypropionic acid Metabolic engineering Glycerol pathway Lignocellulose |
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