Title of article :
Application of metabolome data in functional genomics: A conceptual strategy
Author/Authors :
Wu، نويسنده , , Liang and van Winden، نويسنده , , Wouter A. and van Gulik، نويسنده , , Walter M. and Heijnen، نويسنده , , Joseph J.، نويسنده ,
Issue Information :
دوماهنامه با شماره پیاپی سال 2005
Pages :
9
From page :
302
To page :
310
Abstract :
A gene with yet unknown physiological function can be studied by changing its expression level followed by analysis of the resulting phenotype. This type of functional genomics study can be complicated by the occurrence of ‘silent mutations’, the phenotypes of which are not easily observable in terms of metabolic fluxes (e.g., the growth rate). Nevertheless, genetic alteration may give rise to significant yet complicated changes in the metabolome. We propose here a conceptual functional genomics strategy based on microbial metabolome data, which identifies changes in in vivo enzyme activities in the mutants. These predicted changes are used to formulate hypotheses to infer unknown gene functions. The required metabolome data can be obtained solely from high-throughput mass spectrometry analysis, which provides the following in vivo information: (1) the metabolite concentrations in the reference and the mutant strain; (2) the metabolic fluxes in both strains and (3) the enzyme kinetic parameters of the reference strain. We demonstrate in silico that changes in enzyme activities can be accurately predicted by this approach, even in ‘silent mutants’.
Keywords :
functional genomics , Silent mutations , metabolome , mass spectrometry , flux analysis , Elasticity , Lin-log kinetics
Journal title :
Metabolic Engineering
Serial Year :
2005
Journal title :
Metabolic Engineering
Record number :
1428540
Link To Document :
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