A dynamic metabolite valve for the control of central carbon metabolism

被引:85
|
作者
Solomon, Kevin V. [1 ]
Sanders, Tarielle M. [1 ,2 ]
Prather, Kristala L. J. [1 ]
机构
[1] MIT, Dept Chem Engn, Synthet Biol Engn Res Ctr SynBERC, Cambridge, MA 02139 USA
[2] Norfolk State Univ, Amgens Scholars Program, Dept Chem, Norfolk, VA 23504 USA
基金
美国国家科学基金会;
关键词
Glucose utilization; Flux optimization; Growth mediated buffering; Inverters; Synthetic biology; ESCHERICHIA-COLI K-12; GENE-EXPRESSION; DOWN-REGULATION; PROTEIN; REPRESSION; PATHWAY; DESIGN; GROWTH; OVEREXPRESSION; SESQUITERPENES;
D O I
10.1016/j.ymben.2012.08.006
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Successful redirection of endogenous resources into heterologous pathways is a central tenet in the creation of efficient microbial cell factories. This redirection, however, may come at a price of poor biomass accumulation, reduced cofactor regeneration and low recombinant enzyme expression. In this study, we propose a metabolite valve to mitigate these issues by dynamically tuning endogenous processes to balance the demands of cell health and pathway efficiency. A control node of glucose utilization, glucokinase (Glk), was exogenously manipulated through either engineered antisense RNA or an inverting gene circuit. Using these techniques, we were able to directly control glycolytic flux, reducing the specific growth rate of engineered Escherichia coli by up to 50% without altering final biomass accumulation. This modulation was accompanied by successful redirection of glucose into a model pathway leading to an increase in the pathway yield and reduced carbon waste to acetate. This work represents one of the first examples of the dynamic redirection of glucose away from central carbon metabolism and enables the creation of novel, efficient intracellular pathways with glucose used directly as a substrate. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:661 / 671
页数:11
相关论文
共 50 条
  • [21] Central carbon metabolism of Leishmania parasites
    Saunders, Eleanor C.
    de Souza, David P.
    Naderer, Thomas
    Sernee, Marijke F.
    Ralton, Julie E.
    Doyle, Maria A.
    MacRae, James I.
    Chambers, Jenny L.
    Heng, Joanne
    Nahid, Amsha
    Likic, Vladimir A.
    McConville, Malcolm J.
    PARASITOLOGY, 2010, 137 (09) : 1303 - 1313
  • [22] Isotope-Assisted Metabolite Analysis Sheds Light on Central Carbon Metabolism of a Model Cellulolytic Bacterium Clostridium thermocellum
    Xiong, Wei
    Lo, Jonathan
    Chou, Katherine J.
    Wu, Chao
    Magnusson, Lauren
    Dong, Tao
    Maness, PinChing
    FRONTIERS IN MICROBIOLOGY, 2018, 9
  • [23] CONTROL OF PHOTOSYNTHETIC CARBON METABOLISM
    BASSHAM, JA
    SCIENCE, 1971, 172 (3983) : 526 - &
  • [24] Central control of the metabolism of fats.
    de Langen, CD
    ACTA MEDICA SCANDINAVICA, 1938, 97 : 427 - 439
  • [25] Central nervous system control of metabolism
    Martin G. Myers
    David P. Olson
    Nature, 2012, 491 : 357 - 363
  • [26] Central nervous system control of metabolism
    Myers, Martin G., Jr.
    Olson, David P.
    NATURE, 2012, 491 (7424) : 357 - 363
  • [27] A Role for Astrocytes in the Central Control of Metabolism
    Yi, Chun-Xia
    Habegger, Kirk M.
    Chowen, Julie A.
    Stern, Javier
    Tschoep, Matthias H.
    NEUROENDOCRINOLOGY, 2011, 93 (03) : 143 - 149
  • [28] Toward 'Omic Scale Metabolite Profiling: A Dual Separation-Mass Spectrometry Approach for Coverage of Lipid and Central Carbon Metabolism
    Ivanisevic, Julijana
    Zhu, Zheng-Jiang
    Plate, Lars
    Tautenhahn, Ralf
    Chen, Stephen
    O'Brien, Peter J.
    Johnson, Caroline H.
    Marletta, Michael A.
    Patti, Gary J.
    Siuzdak, Gary
    ANALYTICAL CHEMISTRY, 2013, 85 (14) : 6876 - 6884
  • [29] PROBING CENTRAL CARBON METABOLISM IN PLASMODIUM FALCIPARUM
    Olszewski, Kellen
    Rabinowitz, Joshua D.
    Llinas, Manuel
    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2008, 79 (06): : 364 - 364
  • [30] Central carbon metabolism in the progression of mammary carcinoma
    Adam D. Richardson
    Chen Yang
    Andrei Osterman
    Jeffrey W. Smith
    Breast Cancer Research and Treatment, 2008, 110