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FUNGAL GROWTH 81

such as sodium alginate, carboxymethylcellulose, and
other anionic polymers. They cause fungi to grow as
more dispersed, loosely branched mycelia, perhaps by
binding to hyphae and causing ionic repulsion. This
can be desirable in some industrial processes but not
in others. For example, dispersed filamentous growth
favors the industrial production of fumaric acid by
Rhizopus arrhizusand of pectic enzymes by Aspergillus
niger, but pelleted growth is preferred for industrial
production of itaconic acid and citric acid by A. niger
(Morrin & Ward 1989).

Batch culture versus continuous culture
systems

Batch culture systems are used commonly in industry
because useful primary metabolites such as organic
acids, and secondary metabolites such as antibiotics
(Chapter 7), are produced in the deceleration and
early stationary phases. Batch cultures are also used for
brewing and wine-making, because the culture broth
is the marketable product.
Continuous culture systems (Fig. 4.16) are an altern-
ative to batch culture. In these systems, fresh culture
medium is added at a continuous slow rate, and a
corresponding volume of the old culture medium
together with some of the fungal biomass is removed
by an overflow device. Such culture systems are
monitored automatically so that factors such as pH,
temperature, and dissolved oxygen concentration are
maintained at the desired levels. They are stirred vigor-
ously to keep the organism in suspension and to facilit-
ate diffusion of nutrients and metabolic byproducts.
There are various types of continuous culture system
but the most common type is the chemostat. In this
system the concentrations of nutrients are adjusted
deliberately so that one essential nutrient is at a rel-
atively low concentration while all other components

are present in excess. When the number of cells in

the culture starts to increase, the rate of exponential

growth becomes limited by the growth-limiting nutri-

ent. At this stage the rate of growth of the culture can

be controlled precisely by adjusting the rate at which

fresh culture medium is supplied; this is termed the

dilution rateof the culture. However, it is important

to note that the fungus is always growing exponentially

• only the rateof exponential growth is governed by
  the dilution rate. In theory, by adjusting the dilution
  rate the culture growth rate can be adjusted to any
  desired level, up to μμmax(any further increase in dilu-
  tion rate would cause “wash-out” because the cells
  would be removed by overflow faster than they can
  grow). In practice, however, these cultures become
  unstable as they approach μμmaxbecause then even a
  minor, temporary fluctuation in growth rate can cause
  wash-out.
  Chemostats are useful for many experimental pur-
  poses, because the physiology of fungi can change
  at different growth rates or in response to different
  growth-limiting nutrients. These changes can be
  studied in detail in chemostats whereas they occur
  transiently in batch cultures. For example, when
  Saccharomyces cerevisiaeis grown at low dilution rates
  (slow growth) in glucose-limited culture it uses a sub-
  stantial proportion of the substrate for production of
  biomass. By contrast, S. cerevisiaeproduces ethanol at
  the expense of biomass at higher dilution rates. It
  switches from cell production to alcohol production
  in conditions favoring rapid metabolism, even though
  glucose is the growth-limiting nutrient in both cases.
  Chemostats also are useful for industrial processes,
  because cells or cell products (e.g. antibiotics) can be
  retrieved continuously from the overflow medium.
  In practice, however, most of the traditional industrial
  processes rely on batch cultures, either because the cost
  of converting to continuous culture systems does not
  justify the increased efficiency or because it is difficult
  to design and operate full production-scale chemostat
  systems. The batch cultures used industrially are often
  “fed batch” systems, in which nutrients or other sub-
  strates are added periodically to sustain the production
  of useful metabolites. As we will see in Chapter 7, by
  keeping cells perpetually growth limited in stationary
  phase and then “feeding” the culture with selected
  metabolic precursors, batch cultures can be used to pro-
  duce substantial quantities of antibiotics or other
  commercial products.

Commercial production of fungal biomass

(Quorn™ mycoprotein)

The most interesting recent application of continuous

culture systems has been the development of an entirely

Medium in

Outflow

Stirrer

Hyphae

Cells

Fig. 4.16Diagram of a continuous culture system to pro-
duce fungal biomass.