title: Metabolic engineering of Corynebacterium glutamicum for the production of 3-hydroxypropionic acid from glucose and xylose.
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 38.6g/L, with the yield of 0.48g/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 62.6g/L 3-HP at a yield of 0.51g/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.
authors.affiliation: Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China; Tsinghua Innovation Center in Dongguan, Dongguan 523808, China. Electronic address: zhenchen2013@mail.tsinghua.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wu
authors.affiliation: Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China; Tsinghua Innovation Center in Dongguan, Dongguan 523808, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Liu
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000502:physiology*; D048230:Corynebacterium glutamicum / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D024861:Genetic Enhancement / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D014994:Xylose / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D019344:Lactic Acid; D014994:Xylose; C031601:hydracrylic acid; D005947:Glucose; D005990:Glycerol
keywords: 3-Hydroxypropionic acid; Corynebacterium glutamicum; Glycerol pathway; Lignocellulose; Metabolic engineering