Biology Reference
In-Depth Information
Even setting aside such new speculations, metabolic processes have been adjusted
and tinkered with profitably for some time, and not only for treatment of disease.
Metabolic engineering
is defined as directed modification of cellular metabolism and
properties through the introduction, deletion, and modification of metabolic pathways
by using recombinant DNA and other molecular biological tools. Currently, green
alternatives for many compounds produced chemically using oil are being sought,
as well as more green methods. Biochemical production methods of forcing biologi-
cal organisms or components to overproduce certain desired compounds are one such
alternative, achievable through metabolic engineering. Some of the organisms used as
production hosts include
E. coli
,
Mycobacterium tuberculosis
,
2
and
Saccharomyces
cerevisiae
(yeast). Most of us are quite familiar with the benefits of yeast metabolism,
but, as another example, biochemical engineering processes “feed” glucose and corn
steep liquor to
E. coli
or other bacteria and generate, throughmetabolic processes, suc-
cinic acid, a precursor to production of pharmaceuticals, fine chemicals, biodegradable
polymers, and more. A goal is to understand better the host of metabolic pathways
in organisms, and use this knowledge to increase flux through helpful reactions (so
produce more output) or even to discover previously unsuspected reaction chains that
might produce the desired metabolites in some other fashion. Helpful models would
also allow us to test alternative hypotheses, say by computer, more cheaply than run-
ning multiple experiments, and might give insight into which types of experiments
would be the most useful. One would also hope to obtain a more global perspective,
a
systems perspective
that, for example, allows one to see and predict the effects of
multiple interconnected reactions at a less reductionist level than reaction by reaction.
How might one explore and understand these interconnected reactions, this
bio-
chemical reaction network
, in a systematic and computational way? What does it
mean to have such a system (beyond drawing cartoons)? In order for the cell, and
hence the body as a whole, to be in a living, thriving state, it must generally be able
to maintain some balance (homeostasis). Each reaction will transform a fixed set of
inputs into a fixed set of outputs, but the “flow” or “flux” through a reaction describes
how that transformation or flow through the reaction is occurring. If one focuses on a
portion of these biochemical reactions that form a (sub)network of interest, then in a
balanced state, the total concentration of all chemical compounds in that (sub)system
is not changing. In such a state, what are the chains of reactions for which the “total
flux”, the combined measure of flux in all the reactions, is not changing, i.e., is 0?
It is the exploration of this query and setup
mathematically
, through applying stan-
dard tools from linear algebra to the so-called
stoichiometry matrix
of the reaction
system, that will be the focus of this chapter. In this way, we have an opportunity to
see how a mathematical model for metabolic networks, and certain pathways within
them, can be constructed. Mathematical models like this have the potential to help us
understand, clarify, and make predictions about the very complex inner workings of
2
Note: Tuberculosis infects about 2 billion people—one third of the Earth's population! It's satisfying
to think one can turn this threat on its ear and use knowledge of biology to get
M. tuberculosis
to produce
useful compounds.
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