4
Chapter 1
above mentioned developments in metabolic engineering and systems biology a fundamental
understanding of the cell factory, i.e. how the cells function at different environmental conditions,
has become even more important, not only for design of bioreactions but also to gain detailed
insight into cellular function. Whether one wants to improve a bioprocess or to understand cellular
function at a fundamental level the tools are to a large extent the same. However, as will be
discussed in Chapter 7 the structure of the model used to describe cellular function depends on the
purpose of the study.
What the text does - hopefully in a useful manner - is to integrate the concepts of mathematical
modeling on reasonably general systems with some of the fundamental aspects of microbial
physiology. The cell is the ultimate reactor, and everything that is going to come out of this reactor
has to pass the boundary between the cell and the environment. But what happens inside the cell, in
the
biotic phase
, is intimately coupled with the conditions in the environment, the
abiotic phase.
Therefore the coupling between cell and environment must be given a very serious treatment,
although much idealization is necessary in order to obtain a model of reasonable complexity that
can still be used to study certain general features of bioreactions. The real bioreaction system is an
immensely complicated agglomerate of three phases - gas, liquid, and solid - with concentration
gradients and time constants of greatly different magnitudes. This system is beyond the scope of
any textbook; it is in fact hardly touched upon in front-line research papers. But the individual steps
of a bioreaction, transport to or from the cells, and mixing in a vessel can be treated and will be
illustrated with numerous examples, most of which are simple enough to be solved without
recourse to a computer (and therefore perhaps better suited to impart the understanding of the
underlying mechanisms).
The intended target group for this textbook is students who have studied both natural sciences and
engineering sciences. This includes most students following a chemical engineering curriculum.
Some knowledge of biology will be advantageous, but not mandatory for reading the book. The
book divides the topic into several different themes, as illustrated in Fig. 1.2. It is of little use to
investigate the kinetics of bioreactions without a certain appreciation of the biochemistry of living
organisms. The ingestion of substrate components from the abiotic medium and the fate of a
substrate as it is being converted through metabolic pathways must be known, and the widely
different product distribution under varying environmental conditions must be recognized. Most
chemical engineering students and all microbiologists and biochemists have a working knowledge
of the major pathways of microorganisms. Still, a brief summary of the subject is given in Chapter
2, which at the same time gives an introduction to design of biotech processes. A cursory study of
the many examples dispersed throughout the book may give the impression that
Escherichia coli
,
Saccharomyces cerevisiae
, lactic acid bacteria, and certain filamentous fungi are our favored
microbial species, but it is important to emphasize that the concepts described in this textbook are
equally well suited to analyze also other cellular systems, i.e. other microbes, cell cultures, plants,
animal cells and even human cells.
It is often painful to analyze kinetic data from industrial (or, indeed, academic) research where the
mass balances do not even approximately close. A microorganism grows and produces metabolites
from substrates. Since all the input carbon and nitrogen must be found in one of the effluents from
the bioreactor, the biomass, the remaining substrates or the metabolic products, it appears to be
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