Metabolic engineering

被引:48
作者
Koffas, M [1 ]
Roberge, C [1 ]
Lee, K [1 ]
Stephanopoulos, G [1 ]
机构
[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
关键词
metabolism; flux; pathway;
D O I
10.1146/annurev.bioeng.1.1.535
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Metabolic engineering is the science that combines systematic analysis of metabolic and other pathways with molecular biological techniques to improve cellular properties by designing and implementing rational genetic modifications. As such, metabolic engineering deals with the measurement of metabolic fluxes and elucidation of their control as determinants of metabolic function and cell physiology. A novel aspect of metabolic engineering is that it departs from the traditional reductionist paradigm of cellular metabolism, taking instead a holistic view. In this sense, metabolic engineering is well suited as a framework for the analysis of genome-wide differential gene expression data, in combination with data on protein content and in vivo metabolic fluxes. The insights of the integrated view of metabolism generated by metabolic engineering will have profound implications in biotechnological applications, as well as in devising rational strategies for target selection for screening candidate drugs or designing gene therapies. In this article we review basic concepts of metabolic engineering and provide examples of applications in the production of primary and secondary metabolites, improving cellular properties, and biomedical engineering.
引用
收藏
页码:535 / 557
页数:23
相关论文
共 113 条
[1]   ENHANCEMENT OF TRYPTOPHAN PRODUCTION BY ESCHERICHIA-COLI AS AN APPLICATION OF GENETIC-ENGINEERING [J].
AIBA, S ;
IMANAKA, T ;
TSUNEKAWA, H .
BIOTECHNOLOGY LETTERS, 1980, 2 (12) :525-530
[2]   CLONING OF THE MACROLIDE ANTIBIOTIC BIOSYNTHESIS GENE ACYA, WHICH ENCODES 3-O-ACYLTRANSFERASE, FROM STREPTOMYCES THERMOTOLERANS AND ITS USE FOR DIRECT FERMENTATIVE PRODUCTION OF A HYBRID MACROLIDE ANTIBIOTIC [J].
ARISAWA, A ;
KAWAMURA, N ;
TAKEDA, K ;
TSUNEKAWA, H ;
OKAMURA, K ;
OKAMOTO, R .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 1994, 60 (07) :2657-2660
[3]   TOWARD A SCIENCE OF METABOLIC ENGINEERING [J].
BAILEY, JE .
SCIENCE, 1991, 252 (5013) :1668-1675
[4]   BIOSYNTHESIS OF ANTHRAQUINONES BY INTERSPECIES CLONING OF ACTINORHODIN BIOSYNTHESIS GENES IN STREPTOMYCETES - CLARIFICATION OF ACTINORHODIN GENE FUNCTIONS [J].
BARTEL, PL ;
ZHU, CB ;
LAMPEL, JS ;
DOSCH, DC ;
CONNORS, NC ;
STROHL, WR ;
BEALE, JM ;
FLOSS, HG .
JOURNAL OF BACTERIOLOGY, 1990, 172 (09) :4816-4826
[5]   Glucose and lactate metabolism in C6 glioma cells: Evidence for the preferential utilization of lactate for cell oxidative metabolism [J].
Bouzier, AK ;
Voisin, P ;
Goodwin, R ;
Canioni, P ;
Merle, M .
DEVELOPMENTAL NEUROSCIENCE, 1998, 20 (4-5) :331-338
[6]   STUDIES ON THE UTILIZATION OF LACTOSE BY CORYNEBACTERIUM-GLUTAMICUM, BEARING THE LACTOSE OPERON OF ESCHERICHIA-COLI [J].
BRABETZ, W ;
LIEBL, W ;
SCHLEIFER, KH .
ARCHIVES OF MICROBIOLOGY, 1991, 155 (06) :607-612
[7]   CLONING AND EXPRESSION OF THE STRUCTURAL GENE FOR PYRUVATE DECARBOXYLASE OF ZYMOMONAS-MOBILIS IN ESCHERICHIA-COLI [J].
BRAU, B ;
SAHM, H .
ARCHIVES OF MICROBIOLOGY, 1986, 144 (03) :296-301
[8]   Microbial Conversion of Indene to Indandiol: A Key Intermediate in the Synthesis of CRIXIVAN [J].
Buckland, Barry C. ;
Drew, Stephen W. ;
Connors, Neal C. ;
Chartrain, Michel M. ;
Lee, Chanyong ;
Salmon, Peter M. ;
Gbewonyo, Kodzo ;
Zhou, Weichang ;
Gailliot, Pat ;
Singhvi, Rahul ;
Olewinski, Roger C., Jr. ;
Sun, Wen-Jun ;
Reddy, Jayanthi ;
Zhang, Jinyou ;
Jackey, Barbara A. ;
Taylor, Colleen ;
Goklen, Kent E. ;
Junker, Beth ;
Greasham, Randolph L. .
METABOLIC ENGINEERING, 1999, 1 (01) :63-74
[9]   Metabolic engineering of propanediol pathways [J].
Cameron, DC ;
Altaras, NE ;
Hoffman, ML ;
Shaw, AJ .
BIOTECHNOLOGY PROGRESS, 1998, 14 (01) :116-125