title: Optimum Rebalancing of the 3-Hydroxypropionic Acid Production Pathway from Glycerol in Escherichia coli.
abstract: 3-Hydroxypropionic acid (3-HP) can be biologically produced from glycerol by two consecutive enzymatic reactions, dehydration of glycerol to 3-hydroxypropionaldehyde (3-HPA) and oxidation of 3-HPA. The pathway has been proved efficient, but imbalance between the rates of the two enzymatic reactions often results in the accumulation of the toxic 3-HPA, which severely reduces cell viability and 3-HP production. In this study, we used UTR engineering to maximally increase the activities of glycerol dehydratase (GDHt) and aldehyde dehydrogenase (ALDH) for the high conversion of glycerol to 3-HP. Thereafter, the activity of GDHt was precisely controlled to avoid the accumulation of 3-HPA by varying expression of dhaB1, a gene encoding a main subunit of GDHt. The optimally balanced E. coli HGL_DBK4 showed a substantially enhanced 3-HP titer and productivity compared with the parental strain. The yield on glycerol, 0.97 g 3-HP/g glycerol, in a fed-batch experiment, was the highest ever reported.
authors.affiliation: Department of Chemical Engineering and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology , 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Lim
authors.affiliation: Department of Chemical Engineering and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology , 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Noh
authors.affiliation: Department of Chemical Engineering and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology , 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Jun Hong
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: School of Chemical and Biomolecular Engineering, Pusan National University , 2 Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology , 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Gyoo Yeol
authors.initials: GY
authors.lastname: Jung
mesh_terms: D000444:Aldehyde Dehydrogenase; D015806:Azospirillum brasilense / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D061249:Batch Cell Culture Techniques; D003470:Culture Media / Q000737:chemistry; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D005985:Glyceraldehyde / Q000031:analogs & derivatives / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism*; D006836:Hydro-Lyases; D007218:Industrial Microbiology; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis; D050296:Microbial Viability; D000074041:Microorganisms, Genetically-Modified / Q000235:genetics; D011407:Propane / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D004269:DNA, Bacterial; C047158:3-hydroxypropionaldehyde; D019344:Lactic Acid; D005985:Glyceraldehyde; C031601:hydracrylic acid; D000444:Aldehyde Dehydrogenase; D006836:Hydro-Lyases; C020671:glycerol dehydratase; D005990:Glycerol; D011407:Propane
keywords: 3-hydroxypropionic acid; balancing enzyme activity; metabolic engineering; synthetic biology