Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production

被引:309
作者
Alonso-Gutierrez, Jorge [1 ,2 ]
Chan, Rossana [1 ,2 ]
Batth, Tanveer S. [1 ,2 ]
Adams, Paul D. [1 ,2 ]
Keasling, Jay D. [1 ,2 ,3 ,4 ]
Petzold, Christopher J. [1 ,2 ]
Lee, Taek Soon [1 ,2 ]
机构
[1] Joint Bioenergy Inst, Emeryville, CA 94608 USA
[2] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA
关键词
Limonene; Perillyl alcohol; Mevalonate pathway; Microbial production; Metabolic engineering; Escherichia coli; HETEROLOGOUS MEVALONATE PATHWAY; GENE; PROTEIN; OPTIMIZATION; MONOTERPENES; EXPRESSION; TERPENOIDS; SYNTHASE; THERAPY; PLASMID;
D O I
10.1016/j.ymben.2013.05.004
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
Limonene is a valuable monoterpene used in the production of several commodity chemicals and medicinal compounds. Among them, perillyl alcohol (FOR) is a promising anti-cancer agent that can be produced by hydroxylation of limonene. We engineered E. coli with a heterologous mevalonate pathway and limonene synthase for production of limonene followed by coupling with a cytochrome P450, which specifically hydroxylates limonene to produce FOR. A strain containing all mevalonate pathway genes in a single plasmid produced limonene at titers over 400 mg/L from glucose, substantially higher than has been achieved in the past. Incorporation of a cytochrome P450 to hydroxylate limonene yielded approximately 100 mg/L of FOR. Further metabolic engineering of the pathway and in situ product recovery using anion exchange resins would make this engineered E. cob a potential production platform for any valuable limonene derivative. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:33 / 41
页数:9
相关论文
共 44 条
[31]   Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli [J].
Pitera, Douglas J. ;
Paddon, Chris J. ;
Newman, Jack D. ;
Keasling, Jay D. .
METABOLIC ENGINEERING, 2007, 9 (02) :193-207
[32]   Targeted proteomics for metabolic pathway optimization: Application to terpene production [J].
Redding-Johanson, Alyssa M. ;
Batth, Tanveer S. ;
Chan, Rossana ;
Krupa, Rachel ;
Szmidt, Heather L. ;
Adams, Paul D. ;
Keasling, Jay D. ;
Lee, Taek Soon ;
Mukhopadhyay, Aindrila ;
Petzold, Christopher J. .
METABOLIC ENGINEERING, 2011, 13 (02) :194-203
[33]   Mono and diterpene production in Escherichia coli [J].
Reiling, KK ;
Yoshikuni, Y ;
Martin, VJJ ;
Newman, J ;
Bohlmann, J ;
Keasling, JD .
BIOTECHNOLOGY AND BIOENGINEERING, 2004, 87 (02) :200-212
[34]   Production of the antimalarial drug precursor artemisinic acid in engineered yeast [J].
Ro, DK ;
Paradise, EM ;
Ouellet, M ;
Fisher, KJ ;
Newman, KL ;
Ndungu, JM ;
Ho, KA ;
Eachus, RA ;
Ham, TS ;
Kirby, J ;
Chang, MCY ;
Withers, ST ;
Shiba, Y ;
Sarpong, R ;
Keasling, JD .
NATURE, 2006, 440 (7086) :940-943
[35]   Characterization of the metabolic burden on Escherichia coli DH1 cells imposed by the presence of a plasmid containing a gene therapy sequence [J].
Rozkov, A ;
Avignone-Rossa, CA ;
Ertl, PF ;
Jones, P ;
O'Kennedy, RD ;
Smith, JJ ;
Dale, JW ;
Bushell, ME .
BIOTECHNOLOGY AND BIOENGINEERING, 2004, 88 (07) :909-915
[36]  
Ryder J.A., 2009, AMYRIS BIOTECHNOLOGI
[37]   Absolute quantification of proteins by LCMSE -: A virtue of parallel MS acquisition [J].
Silva, JC ;
Gorenstein, MV ;
Li, GZ ;
Vissers, JPC ;
Geromanos, SJ .
MOLECULAR & CELLULAR PROTEOMICS, 2006, 5 (01) :144-156
[38]   Hydrogenated monoterpenes as diesel fuel additives [J].
Tracy, Noah I. ;
Chen, Daichuan ;
Crunkleton, Daniel W. ;
Price, Geoffrey L. .
FUEL, 2009, 88 (11) :2238-2240
[39]   High-Level Production of Amorpha-4,11-Diene, a Precursor of the Antimalarial Agent Artemisinin, in Escherichia coli [J].
Tsuruta, Hiroko ;
Paddon, Christopher J. ;
Eng, Diana ;
Lenihan, Jacob R. ;
Horning, Tizita ;
Anthony, Larry C. ;
Regentin, Rika ;
Keasling, Jay D. ;
Renninger, Neil S. ;
Newman, Jack D. .
PLOS ONE, 2009, 4 (02)
[40]   Stabilized gene duplication enables long-term selection-free heterologous pathway expression [J].
Tyo, Keith E. J. ;
Ajikumar, Parayil Kumaran ;
Stephanopoulos, Gregory .
NATURE BIOTECHNOLOGY, 2009, 27 (08) :760-U115