The role of metabolic engineering in the production of secondary metabolites

被引:30
作者
Nielsen, J [1 ]
机构
[1] Tech Univ Denmark, Dept Biotechnol, Ctr Proc Biotechnol, DK-2800 Lyngby, Denmark
关键词
D O I
10.1016/S1369-5274(98)80037-4
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In the production of secondary metabolites yield and productivity are the most important design parameters. The focus is therefore to direct the carbon fluxes towards the product of interest, and this can be obtained through metabolic engineering whereby directed genetic changes are introduced into the production strain. In this process it is, however, important to analyze the metabolic network through measurement of the intracellular metabolites and the flux distributions. Besides playing an important role in the optimization of existing processes, metabolic engineering also offers the possibility to construct strains that produce novel metabolites, either through the recruitment of heterologous enzyme activities or through introduction of specific mutations in catalytic activities.
引用
收藏
页码:330 / 336
页数:7
相关论文
共 45 条
[1]   TOWARD A SCIENCE OF METABOLIC ENGINEERING [J].
BAILEY, JE .
SCIENCE, 1991, 252 (5013) :1668-1675
[2]   LARGE AMPLIFICATION OF A 35-KB DNA FRAGMENT CARRYING 2 PENICILLIN BIOSYNTHETIC GENES IN HIGH PENICILLIN PRODUCING STRAINS OF PENICILLIUM-CHRYSOGENUM [J].
BARREDO, JL ;
DIEZ, B ;
ALVAREZ, E ;
MARTIN, JF .
CURRENT GENETICS, 1989, 16 (5-6) :453-459
[3]   A functional chimeric modular polyketide synthase generated via domain replacement [J].
Bedford, D ;
Jacobsen, JR ;
Luo, GL ;
Cane, DE ;
Khosla, C .
CHEMISTRY & BIOLOGY, 1996, 3 (10) :827-831
[4]   CELLULAR AND METABOLIC ENGINEERING - AN OVERVIEW [J].
CAMERON, DC ;
TONG, IT .
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY, 1993, 38 (1-2) :105-140
[5]   ISOLATION OF DEACETOXYCEPHALOSPORIN-C FROM FERMENTATION BROTHS OF PENICILLIUM-CHRYSOGENUM TRANSFORMANTS - CONSTRUCTION OF A NEW FUNGAL BIOSYNTHETIC-PATHWAY [J].
CANTWELL, C ;
BECKMANN, R ;
WHITEMAN, P ;
QUEENER, SW ;
ABRAHAM, EP .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1992, 248 (1323) :283-289
[6]   PRODUCTION OF CEPHALOSPORIN INTERMEDIATES BY FEEDING ADIPIC ACID TO RECOMBINANT PENICILLIUM-CHRYSOGENUM STRAINS EXPRESSING RING EXPANSION ACTIVITY [J].
CRAWFORD, L ;
STEPAN, AM ;
MCADA, PC ;
RAMBOSEK, JA ;
CONDER, MJ ;
VINCI, VA ;
REEVES, CD .
BIO-TECHNOLOGY, 1995, 13 (01) :58-62
[7]  
DIEZ B, 1990, J BIOL CHEM, V265, P16358
[8]   AN ERYTHROMYCIN ANALOG PRODUCED BY REPROGRAMMING OF POLYKETIDE SYNTHESIS [J].
DONADIO, S ;
MCALPINE, JB ;
SHELDON, PJ ;
JACKSON, M ;
KATZ, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) :7119-7123
[9]   MODULAR ORGANIZATION OF GENES REQUIRED FOR COMPLEX POLYKETIDE BIOSYNTHESIS [J].
DONADIO, S ;
STAVER, MJ ;
MCALPINE, JB ;
SWANSON, SJ ;
KATZ, L .
SCIENCE, 1991, 252 (5006) :675-679
[10]   METABOLIC CONTROL ANALYSIS - A SURVEY OF ITS THEORETICAL AND EXPERIMENTAL DEVELOPMENT [J].
FELL, DA .
BIOCHEMICAL JOURNAL, 1992, 286 :313-330