Improving lycopene production in Escherichia coli by engineering metabolic control

Nature Biotechnology
W R Farmer, J C Liao


Metabolic engineering has achieved encouraging success in producing foreign metabolites in a variety of hosts. However, common strategies for engineering metabolic pathways focus on amplifying the desired enzymes and deregulating cellular controls. As a result, uncontrolled or deregulated metabolic pathways lead to metabolic imbalance and suboptimal productivity. Here we have demonstrated the second stage of metabolic engineering effort by designing and engineering a regulatory circuit to control gene expression in response to intracellular metabolic states. Specifically, we recruited and altered one of the global regulatory systems in Escherichia coli, the Ntr regulon, to control the engineered lycopene biosynthesis pathway. The artificially engineered regulon, stimulated by excess glycolytic flux through sensing of an intracellular metabolite, acetyl phosphate, controls the expression of two key enzymes in lycopene synthesis in response to flux dynamics. This intracellular control loop significantly enhanced lycopene production while reducing the negative impact caused by metabolic imbalance. Although we demonstrated this strategy for metabolite production, it can be extended into other fields where gene expression must be cl...Continue Reading


Dec 18, 2001·Biotechnology and Bioengineering·W R Farmer, J C Liao
Dec 14, 2004·Biotechnology and Bioengineering·Kapil G GadkarRadhakrishnan Mahadevan
Sep 1, 2005·Applied Microbiology and Biotechnology·Luan TaoQiong Cheng
Oct 7, 2008·Applied Microbiology and Biotechnology·Hisashi HaradaNorihiko Misawa
Sep 4, 2009·Applied Microbiology and Biotechnology·Jin Hou, Goutham N Vemuri
Oct 28, 2009·Applied Microbiology and Biotechnology·Anthony F Cann, James C Liao
Apr 17, 2010·Applied Microbiology and Biotechnology·Heinz Neumann, Petra Neumann-Staubitz
Nov 29, 2012·Applied Microbiology and Biotechnology·Chuan XuMing Chen
Feb 10, 2009·Journal of Industrial Microbiology & Biotechnology·Yajun Yan, James C Liao
Feb 14, 2012·Journal of Industrial Microbiology & Biotechnology·Sambandam RavikumarSoon Ho Hong
Sep 2, 2010·Systems and Synthetic Biology·Mary J DunlopAindrila Mukhopadhyay
Jun 19, 2010·Applied Biochemistry and Biotechnology·Han Seung ChaePyung Cheon Lee
Mar 9, 2011·Theory in Biosciences = Theorie in Den Biowissenschaften·Vic NorrisAlain R Thierry
May 20, 2011·Biochemistry·Amy M Weeks, Michelle C Y Chang
Aug 10, 2000·Nature Biotechnology·J M Jez, J P Noel
May 6, 2005·Nature·Eileen FungJames C Liao
Jul 28, 2009·Nature Biotechnology·Keith E J TyoGregory Stephanopoulos
Jul 2, 2004·Nature Biotechnology·James C Liao
Oct 8, 2004·Nature Biotechnology·Gregory StephanopoulosJoel Moxley
May 20, 2006·Nature Chemical Biology·Jason W Chin
Sep 17, 2009·Nature Reviews. Microbiology·Hal Alper, Gregory Stephanopoulos
Dec 30, 2010·Nature Reviews. Microbiology·Marnix H MedemaEriko Takano
Nov 15, 2007·Molecular BioSystems·Daniel J SayutLianhong Sun
Feb 28, 2001·The EMBO Journal·I Cases, V de Lorenzo
Mar 9, 2013·Nucleic Acids Research·Lior ZelcbuchRon Milo
Oct 12, 2012·Journal of the Royal Society, Interface·Diego A Oyarzún, Guy-Bart V Stan
Oct 12, 2010·Science·Parayil Kumaran AjikumarGregory Stephanopoulos
Dec 4, 2010·Science·Jay D Keasling
Mar 30, 2010·Applied and Environmental Microbiology·Hyung Seok ChoiHan Min Woo
Aug 5, 2008·Applied and Environmental Microbiology·Michael R Connor, James C Liao
Aug 7, 2012·Applied and Environmental Microbiology·Guo-Shu WangRobin Ghosh
Oct 16, 2007·Applied and Environmental Microbiology·T HanaiJ C Liao
Jan 9, 2007·Applied and Environmental Microbiology·Igor HernándezJohan E T van Hylckama Vlieg
Jul 4, 2003·Applied and Environmental Microbiology·Jan C VerdoesAlbert J J van Ooyen
Jun 10, 2005·Microbiology and Molecular Biology Reviews : MMBR·Goutham N Vemuri, Aristos A Aristidou
Apr 7, 2010·Annual Review of Biochemistry·Jeffrey A DietrichJay D Keasling
Feb 19, 2013·Annual Review of Chemical and Biomolecular Engineering·Yen-Hsiang WangChristina D Smolke
Jan 1, 2010·Annual Review of Chemical and Biomolecular Engineering·Han LiJames C Liao
Sep 10, 2010·Journal of Biomedicine & Biotechnology·Michael R Connor, Shota Atsumi
Mar 20, 2008·Journal of Molecular Microbiology and Biotechnology·Pablo I NikelBeatriz S Méndez
Aug 27, 2005·Microbial Cell Factories·Tanya Warnecke, Ryan T Gill
Jan 22, 2010·Microbial Cell Factories·Clementina DellomonacoRamon Gonzalez
Jul 2, 2009·BMC Systems Biology·Bor-Sen Chen, Chih-Hung Wu


Dec 1, 1992·Journal of Bacteriology·R PatnaikJ C Liao
Jun 21, 1991·Science·J E Bailey
Apr 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·L J Reitzer, B Magasanik
Jul 1, 1996·Molecular Microbiology·C G Kurland, H Dong
Aug 1, 1997·Applied and Environmental Microbiology·W R Farmer, J C Liao
Aug 1, 1997·Applied Microbiology and Biotechnology·A RutherGerhard Sandmann
Apr 18, 1998·Applied and Environmental Microbiology·Y MiuraNorihiko Misawa
May 30, 1998·Proceedings of the Society for Experimental Biology and Medicine·H Sies, W Stahl
Mar 2, 1999·Journal of the National Cancer Institute·E Giovannucci
Apr 1, 1999·Biotechnology and Bioengineering·C W WangJ C Liao
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·I HwangY K Shin
Feb 20, 1997·Biotechnology and Bioengineering·N DedhiaW Chen

Related Concepts

Metabolic Process, Cellular
Gene Expression Regulation, Bacterial
Biochemical Pathway
acetyl phosphate
Bacterial Proteins
Gene Dosage
Alkalescens-Dispar Group
Enzymes, antithrombotic

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