Engineering Cellular Metabolism

被引:907
作者
Nielsen, Jens [1 ,2 ,3 ]
Keasling, Jay D. [2 ,4 ,5 ,6 ,7 ,8 ]
机构
[1] Chalmers Univ Technol, Dept Biol & Biol Engn, Kemivagen 10, SE-41296 Gothenburg, Sweden
[2] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2970 Horsholm, Denmark
[3] Royal Inst Technol, Sci Life Lab, SE-17121 Solna, Sweden
[4] Joint Bioenergy Inst, Emeryville, CA 94608 USA
[5] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA
[6] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
[7] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA 94720 USA
[8] Synthet Biol Engn Res Ctr Synberc, Berkeley, CA 94720 USA
基金
美国国家科学基金会;
关键词
TRANSCRIPTIONAL REGULATORY NETWORKS; HIGH-LEVEL PRODUCTION; DE-NOVO PRODUCTION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; PATHWAY OPTIMIZATION; MICROBIAL-PRODUCTION; YEAST; EXPRESSION; PLATFORM;
D O I
10.1016/j.cell.2016.02.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.
引用
收藏
页码:1185 / 1197
页数:13
相关论文
共 111 条
[1]   Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli [J].
Ajikumar, Parayil Kumaran ;
Xiao, Wen-Hai ;
Tyo, Keith E. J. ;
Wang, Yong ;
Simeon, Fritz ;
Leonard, Effendi ;
Mucha, Oliver ;
Phon, Too Heng ;
Pfeifer, Blaine ;
Stephanopoulos, Gregory .
SCIENCE, 2010, 330 (6000) :70-74
[2]   Principal component analysis of proteomics (PCAP) as a tool to direct metabolic engineering [J].
Alonso-Gutierrez, Jorge ;
Kim, Eun-Mi ;
Batth, Tanveer S. ;
Cho, Nathan ;
Hu, Qijun ;
Chan, Leanne Jade G. ;
Petzold, Christopher J. ;
Hinson, Nathan J. ;
Adams, Paul D. ;
Keasling, Jay D. ;
Martin, Hector Garcia ;
Lee, Taek Soon .
METABOLIC ENGINEERING, 2015, 28 :123-133
[3]   Global transcription machinery engineering: A new approach for improving cellular phenotype [J].
Alper, Hal ;
Stephanopoulos, Gregory .
METABOLIC ENGINEERING, 2007, 9 (03) :258-267
[4]  
[Anonymous], FEMS YEAST RES
[5]   Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols [J].
Avalos, Jose L. ;
Fink, Gerald R. ;
Stephanopoulos, Gregory .
NATURE BIOTECHNOLOGY, 2013, 31 (04) :335-+
[6]   TOWARD A SCIENCE OF METABOLIC ENGINEERING [J].
BAILEY, JE .
SCIENCE, 1991, 252 (5013) :1668-1675
[7]   Random Mutagenesis of the Pm Promoter as a Powerful Strategy for Improvement of Recombinant-Gene Expression [J].
Bakke, Ingrid ;
Berg, Laila ;
Aune, Trond Erik Vee ;
Brautaset, Trygve ;
Sletta, Havard ;
Tondervik, Anne ;
Valla, Svein .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2009, 75 (07) :2002-2011
[8]   Growth-limiting Intracellular Metabolites in Yeast Growing under Diverse Nutrient Limitations [J].
Boer, Viktor M. ;
Crutchfield, Christopher A. ;
Bradley, Patrick H. ;
Botstein, David ;
Rabinowitz, Joshua D. .
MOLECULAR BIOLOGY OF THE CELL, 2010, 21 (01) :198-211
[9]   Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production [J].
Brynildsen, Mark P. ;
Winkler, Jonathan A. ;
Spina, Catherine S. ;
MacDonald, I. Cody ;
Collins, James J. .
NATURE BIOTECHNOLOGY, 2013, 31 (02) :160-165
[10]   Altered sterol composition renders yeast thermotolerant [J].
Caspeta, Luis ;
Chen, Yun ;
Ghiaci, Payam ;
Feizi, Amir ;
Buskov, Steen ;
Hallstrom, Bjorn M. ;
Petranovic, Dina ;
Nielsen, Jens .
SCIENCE, 2014, 346 (6205) :75-78