title: High Production of 3-Hydroxypropionic Acid in Klebsiella pneumoniae by Systematic Optimization of Glycerol Metabolism.
abstract: 3-Hydroxypropionic acid (3-HP) is an important platform chemical proposed by the United States Department of Energy. 3-HP can be converted to a series of bulk chemicals. Biological production of 3-HP has made great progress in recent years. However, low yield of 3-HP restricts its commercialization. In this study, systematic optimization was conducted towards high-yield production of 3-HP in Klebsiella pneumoniae. We first investigated appropriate promoters for the key enzyme (aldehyde dehydrogenase, ALDH) in 3-HP biosynthesis, and found that IPTG-inducible tac promoter enabled overexpression of an endogenous ALDH (PuuC) in K. pneumoniae. We optimized the metabolic flux and found that blocking the synthesis of lactic acid and acetic acid significantly increased the production of 3-HP. Additionally, fermentation conditions were optimized and scaled-up cultivation were investigated. The highest 3-HP titer was observed at 83.8 g/L with a high conversion ratio of 54% on substrate glycerol. Furthermore, a flux distribution model of glycerol metabolism in K. pneumoniae was proposed based on in silico analysis. To our knowledge, this is the highest 3-HP production in K. pneumoniae. This work has significantly advanced biological production of 3-HP from renewable carbon sources.
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.|College of Biochemical Engineering, Beijing Union University, Beijing 100023, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Biochemical Engineering, Beijing Union University, Beijing 100023, People's Republic of China.
authors.forename: Xizhen
authors.initials: X
authors.lastname: Ge
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
authors.forename: Pingfang
authors.initials: P
authors.lastname: Tian
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005285:Fermentation; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005990:Glycerol / Q000378:metabolism*; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis; D060847:Metabolic Engineering; D011401:Promoter Regions, Genetic
chemical_list: D001426:Bacterial Proteins; D019344:Lactic Acid; D007544:Isopropyl Thiogalactoside; C031601:hydracrylic acid; D000444:Aldehyde Dehydrogenase; D005990:Glycerol; D019342:Acetic Acid