Model-independent fluxome profiling from 2H and 13C experiments for metabolic variant discrimination -: art. no. R99

被引:22
作者
Zamboni, N [1 ]
Sauer, U [1 ]
机构
[1] ETH, Inst Biotechnol, CH-8093 Zurich, Switzerland
关键词
D O I
10.1186/gb-2004-5-12-r99
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
We introduce a conceptually novel method for intracellular fluxome profiling from unsupervised statistical analysis of stable isotope labeling. Without a priori knowledge on the metabolic system, we identified characteristic flux fingerprints in 10 Bacillus subtilis mutants from 132 H-2 and C-13 tracer experiments. Beyond variant discrimination, independent component analysis automatically mapped several fingerprints to their metabolic determinants. The approach is flexible and paves the way to large-scale fluxome profiling of any biological system and condition.
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页数:12
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共 37 条
[1]   High-throughput classification of yeast mutants for functional genomics using metabolic footprinting [J].
Allen, J ;
Davey, HM ;
Broadhurst, D ;
Heald, JK ;
Rowland, JJ ;
Oliver, SG ;
Kell, DB .
NATURE BIOTECHNOLOGY, 2003, 21 (06) :692-696
[2]   Lessons from metabolic engineering for functional genomics and drug discovery [J].
Bailey, JE .
NATURE BIOTECHNOLOGY, 1999, 17 (07) :616-618
[3]   Independent component analysis at the neural cocktail party [J].
Brown, GD ;
Yamada, S ;
Sejnowski, TJ .
TRENDS IN NEUROSCIENCES, 2001, 24 (01) :54-63
[4]   Bacillus subtilis metabolism and energetics in carbon-limited and excess-carbon chemostat culture [J].
Dauner, M ;
Storni, T ;
Sauer, U .
JOURNAL OF BACTERIOLOGY, 2001, 183 (24) :7308-7317
[5]   Regulation of the central glycolytic genes in Bacillus subtilis:: binding of the repressor CggR to its single DNA target sequence is modulated by fructose-1,6-bisphosphate [J].
Doan, T ;
Aymerich, S .
MOLECULAR MICROBIOLOGY, 2003, 47 (06) :1709-1721
[6]   Methods for intense aeration, growth, storage, and replication of bacterial strains in microtiter plates [J].
Duetz, WA ;
Rüedi, L ;
Hermann, R ;
O'Connor, K ;
Büchs, J ;
Witholt, B .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2000, 66 (06) :2641-2646
[7]   Metabolite profiling for plant functional genomics [J].
Fiehn, O ;
Kopka, J ;
Dörmann, P ;
Altmann, T ;
Trethewey, RN ;
Willmitzer, L .
NATURE BIOTECHNOLOGY, 2000, 18 (11) :1157-1161
[8]   Two glyceraldehyde-3-phosphate dehydrogenases with opposite physiological roles in a nonphotosynthetic bacterium [J].
Fillinger, S ;
Boschi-Muller, S ;
Azza, S ;
Dervyn, E ;
Branlant, G ;
Aymerich, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (19) :14031-14037
[9]   Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS [J].
Fischer, E ;
Sauer, U .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2003, 270 (05) :880-891
[10]   High-throughput metabolic flux analysis based on gas chromatography-mass spectrometry derived 13C constraints [J].
Fischer, E ;
Zamboni, N ;
Sauer, U .
ANALYTICAL BIOCHEMISTRY, 2004, 325 (02) :308-316