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interleukin-12b chain (serine content of 11.1%), as well. These examples
demonstrate that the strategy of local pathway engineering based
on global information (proteome profiling in the above examples) is
highly efficient for strain improvement.
Metabolome Analysis
The general aims of metabolomics are to identify metabolites and
quantitatively determine their concentrations. Various quantitative tools
for identifying and analyzing cellular metabolites have been developed
to investigate the detailed metabolic status of cells [33]. High-throughput
quantitative analysis of metabolites has become possible with the
development of increasingly sophisticated gas chromatography-mass
spectrometry (GC-MS), gas chromatography time-of-flight mass
spectrometry (GC-TOF), liquid chromatography-mass spectrometry
(LC-MS), and nuclear magnetic resonance (NMR) equipment. No single
technique is suitable for the analysis of all different types of molecule,
so a mixture of techniques is used. The diversity of methods ensures
broad coverage of a wide range of different classes of organic compounds.
Even though much effort is needed to solve existing problems such
as the limited number of metabolites detectable and the accuracy
of metabolite concentrations measured, there have been some success-
ful uses of metabolome profiling in analyzing cellular metabolism.
Villas-Boas et al. [34] reported the application of a novel derivatization
method for metabolome analysis in yeasts. A method was developed to
simultaneously measure the metabolites throughout the central carbon
metabolism and amino acid biosynthetic pathways using GC-MS. As
model systems, they assayed the metabolite levels for two yeast strains
and two different culture conditions; the changing levels of many
metabolites caused by the genetic ( gdh1 knockout) and environmental
(aerobic and anaerobic) perturbations were examined. By comparing
the metabolite levels throughout the samples, it was possible to identify
the activated genes or metabolic pathways. This study demonstrates
the true power of metabolome analysis in understanding specific
metabolic pathways and provides new insight into the integrated tran-
scription-metabolism studies. There has been another interesting
report on the combined analysis of the transcriptome and metabolome
for understanding the metabolic characteristics of Aspergillus produc-
ing lovastatin and consequently for the development of improved
strains, as will be seen below. As our ability to quantitatively analyze
the metabolites increases, metabolome profiling will become an indis-
pensable tool for the analysis and engineering of metabolic pathways.
Combined X-omes Analysis for Strain Improvements
Even though the true integration of all x-omic data is not yet possible
at this time, local information extracted from these global-scale data
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