Fed-Batch Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 683

An example of fed-batch culture is its use in some antibiotic fermentations, where
a glucose solution is intermittently added to the fermentation broth due to the repression
or inhibition of pathways for the production of secondary metabolites caused by high initial
glucose concentrations. Fed-batch operations can be applied to other secondary metabolite
fermentations such as lactic acid and other plant cell and mammalian cell fermentations,
where the rate of product generation is maximal at low concentrations while chemostat
is not suitable.
Fed-batch culturing is an important technique for E. coli cultivation to make proteins from
recombinant DNA technology. To make high concentration of product, high substrate
(glucose) is needed. However, with unlimited supply of substrate or at high glucose concen-
tration, E. coli will grow at a maximum rate but produce organic acids (e.g. acetic acid) as by-
products. The accumulation of these by-products inhibits growth. If glucose is fed at a rate
that sustains the growth rate at slightly less than optimal, E. coli uses the glucose more effi-
ciently and makes less by-products. Very high cell densities (50 100 g/L) can be achieved.

Fed-batch fermentations, due to an inherent flexibility of the method, provide a valuable
tool in biotechnology, not only to study microorganism physiology but also to commercially
produce valuable components. The higher productivities of fed-batch as compared with
batch and the technical problems of continuous cultures, fed-batch seems to be a technique
with increasing importance in bioreactor operations.

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13.4. ADVANTAGES AND DISADVANTAGES OF FED-BATCH
OPERATIONS

As we have seen that fed-batch fermentation is a production technique in between batch
and continuous fermentation. A proper feed rate, with the right component constitution, is
required during the process.
Fed-batch offers many advantages over batch and continuous cultures. From the concept
of its implementation, it can be easily concluded that under controllable conditions and with
the required knowledge of the microorganism involved in the fermentation, the feed of the
required components for growth and/or other substrates required for the production of
the product can never be depleted and the nutritional environment can be maintained
approximately constant during the course of the batch. The production of by-products that
are generally related to the presence of high concentrations of the substrate can also be
avoided by limiting its concentration to the level that are required solely for the production
of the desired biochemical. When high concentrations of the substrate are present, the cells
get “overloaded”, that is, the oxidative capacity of the cells is exceeded, and due to the
Crabtree effect, products other than the one of interest are produced, reducing the efficacy
of the carbon flux. Moreover, these by-products “contaminate” the desired product, such
as ethanol production in baker's yeast production and to impair the cell growth reducing
the fermentation time and its related productivity.
Sometimes, controlling the substrate is also important due to catabolic repression. Since
this method usually permits the extension of the operating time, high cell concentrations
can be achieved, and thereby, improved productivity (mass of the product produced per