Systems Biology and Metabolic Engineering in Bacteria - Systems Biology of Metabolic and Signaling Networks - page 342

Fig. 13.1 The central role of the metabolic network. The metabolic network is central to a systems
biology description of organism functioning. Numerous data sources, genetic, biochemical, and
-omics data, are combined to construct a biochemical reaction network. This network describes
all possible transformations between the metabolites ( blue circles ) of the organism. The
transformations include inflow (e.g., glucose uptake) and outflow (e.g., acetate secretion) reactions
symbolized by arrows without starting or ending metabolite. The reaction network forms the basis
for all further analyses, from a topological description of the network to dynamical simulations and
parameter estimation by comparison with experimental data
(1) understanding the functioning of the organism as a whole and (2) exploiting this
knowledge for applications in biotechnology and synthetic biology.
The basis for understanding the functioning of microbial metabolism is a
complete knowledge of the underlying metabolic network, i.e., the metabolites
and the enzymes that interconvert these metabolites (Fig. 13.1 ). The next section
argues that current -omics techniques have essentially achieved this goal. Based
on this map, we can investigate the functional properties of the network at two
levels: (1) during balanced growth, a hallmark of microbial physiology and
(2) at transitions between different conditions, the “normal” lifestyle of most
microorganisms. Finally, the metabolic network is, of course, not isolated in the
cell, but embedded in a complex control structure involving metabolic, genetic, and
posttranslational control mechanisms. Much progress has been made recently to
incorporate all these interactions into integrated models, culminating in whole-cell
models of an entire bacterium (Karr et al. 2012b ). These models are not solely
intellectual tools for understanding the functioning of an organism; they also form
the basis of many applications in biotechnology (Feist and Palsson 2008 ).
13.2 Maps of Metabolic Networks in Bacteria
The first step in network reconstruction is the establishment of a reliable model of
the network, i.e., identifying all components (metabolites) and their connections
(enzymes and their reactions). The first metabolic models of the beginning of the
1990s were of limited scope, focusing, for example, on amino acid and nucleotide
metabolism. The advent of the genomic era in the late 1990 has greatly contributed
to the fast growth of the number and size of metabolic models (Kim et al. 2012 ).
Numerous software tools have now been developed to help deriving a network