F
Fatty Acids see Fermentation (Industrial): Production of Oils and Fatty Acids.
FERMENTATION (INDUSTRIAL)
Contents
Basic Considerations
Media for Industrial Fermentations
Control of Fermentation Conditions
Recovery of Metabolites
Production of Xanthan Gum
Production of Organic Acids Production of
Oils and Fatty Acids Colours/Flavours
Derived by Fermentation
dissolved substrate, e.g. sugar solution, or a solid
Basic Considerations substrate, suspended in a large amount of water to
Vusuf Chisti, Department of Chemical Engineering, form a slurry. Submerged fermentations are used for
University of Almeria, Spain pickling vegetables, producing yoghurt, brewing beer
and producing wine and soy sauce.
Copyright 1999 Academic Press Solid-state and submerged fermentations may each
be subdivided - into oxygen-requiring aerobic pro
Introduction cesses, and anaerobic processes that must be con
ducted in the absence of oxygen. Examples of aerobic
Fermentation processes utilize microorganisms to fermentations include submerged-culture citric acid
convert solid or liquid substrates into various prod production by Aspergillus niger and solid-state koji
ucts. The substrates used vary widely, any material fermentations (used in the production of soy sauce).
that supports microbial growth being a potential sub Fermented meat products such as bologna sausage
strate. Similarly, fermentation-derived products show (polony), dry sausage, pepperoni and salami are pro
tremendous variety. Commonly consumed fermented duced by solid-state anaerobic fermentations utilizing
products include bread, cheese, sausage, pickled vege acid-forming bacteria, particularly Lactobacillus,
tables, cocoa, beer, wine, citric acid, glutamic acid Pediococcus and Micrococcus species. A submerged
and soy sauce. culture anaerobic fermentation occurs in yoghurt
making.
Types of Fermentation
Fermentations may require only a single species of
Most commercially useful fermentations may be clas microorganism to effect the desired chemical change.
sified as either solid-state or submerged cultures. In In this case the substrate may be sterilized, to kill
solid-state fermentations, the microorganisms grow unwanted species prior to inoculation with the desired
on a moist solid with little or no 'free' water, although microorganism. However, most food fermentations
capillary water may be present. Examples of this type are non-sterile. Typically fermentations used in food
of fermentation are seen in mushroom cultivation, processing require the participation of several micro
bread-making and the processing of cocoa, and in the bial species, acting simultaneously and/or sequen
manufacture of some traditional foods, e.g. miso (soy tially, to give a product with the desired properties,
paste), sake, soy sauce, tempeh (soybean cake) and including appearance, aroma, texture and taste. In
gari (cassava), which are now produced in large indus non-sterile fermentations, the culture environment
trial operations. Submerged fermentations may use a
Chisti, Y., in Encyclopedia of Food Microbiology, Robinson, R., Batt, C., and Patel, P., editors, Academic Press, London,
1999, pp. 663-674. Fermentation (industrial): Basic considerations.
664 FERMENTATION (INDUSTRIAL)/Basic Considerations
may be tailored specifically to favour the desired fermentation batch. The volume of the fermenting
microorganisms. For example, the salt content may broth increases with each addition of the medium, and
be high, the pH may be low, or the water activity may the fermenter is harvested after the batch time.
be reduced by additives such as salt or sugar. In continuous fermentations, sterile medium is fed
continuously into a fermenter and the fermented
Factors Influencing Fermentations
product is continuously withdrawn, so the fer
A fermentation is influenced by numerous factors, mentation volume remains unchanged. Typically, con
including temperature, pH, nature and composition tinuous fermentations are started as batch cultures
of the medium, dissolved 02, dissolved C02, oper and feeding begins after the microbial population has
ational system (e.g. batch, fed-batch, continuous), reached a certain concentration. In some continuous
feeding with precursors, mixing (cycling through fermentations, a small part of the harvested culture
varying environments), and shear rates in the fer may be recycled, to continuously inoculate the sterile
menter. Variations in these factors may affect: the rate feed medium entering the fermenter (Fig. l(D)).
of fermentation; the product spectrum and yield; the Whether continuous inoculation is necessary depends
organoleptic properties of the product (appearance, on the type of mixing in the fermenter. 'Plug flow'
taste, smell and texture); the generation of toxins; fermentation devices (Fig. l(D)), such as long tubes
nutritional quality; and other physico-chemical that do not allow back mixing, must be inoculated
properties. continuously. Elements of fluid moving along in a
The formulation of the fermentation medium plug flow device behave like tiny batch fermenters.
affects the yield, rate and product profile. The medium Hence, true batch fermentation processes are rela
must provide the necessary amounts of carbon, nitro tively easily transformed into continuous operations
gen, trace elements and micronutrients (e.g. vitamins). in plug flow fermenters, especially if pH control and
Specific types of carbon and nitrogen sources may be aeration are not required. Continuous cultures are
required, and the carbon:nitrogen ratio may have particularly susceptible to microbial contamination,
to be controlled. An understanding of fermentation but in some cases the fermentation conditions may be
biochemistry is essential for developing a medium selected (e.g. low pH, high alcohol or salt content)
with an appropriate formulation. Concentrations of to favour the desired microorganisms compared to
certain nutrients may have to be varied in a specific potential contaminants.
way during a fermentation to achieve the desired In a 'well-mixed' continuous fermenter (Fig. l(C)),
result. Some trace elements may have to be avoided the feed rate of the medium should be such that the
for example, minute amounts of iron reduce yields in dilution rate, i.e. the ratio of the volumetric feed rate
citric acid production by Aspergillus niger. Additional to the constant culture volume, remains less than the
factors, such as cost, availability, and batch-to-batch maximum specific growth rate of the microorganism
variability also affect the choice of medium.
in the particular medium and at the particular fer
mentation conditions. If the dilution rate exceeds the
Submerged Fermentations maximum specific growth rate, the microorganism
will be washed out of the fermenter.
Fermentation Systems Industrial fermentations are mostly batch oper
Industrial fermentations may be carried out either ations.Typically, a pure starter culture (or seed), main
batchwise, as fed-batch operations, or as continuous tained under carefully controlled conditions, is used
cultures (Fig. 1). Batch and fed-batch operations are to inoculate sterile Petri dishes or liquid medium in the
quite common, continuous fermentations being rela shake flasks. After sufficient growth, the pre-culture is
tively rare. For example, continuous brewing is used used to inoculate the 'seed' fermenter. Because indus
commercially, but most beer breweries use batch trial fermentations tend to be large (typically 150-
processes. 250 m 3), the inoculum is built up through several
In batch processing, a batch of culture medium in successively larger stages, to 5-l0% of the working
a fermenter is inoculated with a microorganism (the volume of the production fermenter. A culture in rapid
'starter culture'). The fermentation proceeds for a exponential growth is normally used for inoculation.
certain duration (the 'fermentation time' or 'batch Slower-growing microorganisms require larger
time'), and the product is harvested. Batch fer inocula, to reduce the total duration of the fer
mentations typically extend over 4-5 days, but some mentation. An excessively long fermentation time (or
traditional food fermentations may last months. In fed batch time) reduces productivity (amount of product
batch fermentations, sterile culture medium is added produced per unit time per unit volume of fermenter),
either continuously or periodically to the inoculated and increases costs. Sometimes inoculation spores,
Feed
Constant
volume Initial volume
Feed T Harvest
Recycle inoculum
Figure 1 Fermentation methodologies. (A) Batch fermentation. (B) Fed-batch culture. (C) Continuous-flow well-mixed fermentation.
(D) Continuous plug flow fermentation, with and without recycling of inoculum.
produced as seeds, are blown directly into large fer nutrients are exhausted and inhibitory products of
mentation vessels with the ingoing air. metabolism build up, the culture enters a stationary
phase. Ultimately, starvation causes cell death and
Microbial Growth lysis, and hence the biomass concentration declines.
Microbial growth in a newly inoculated batch fer Exponential growth can be described by Equation
menter typically follows the pattern shown in Figure 1:
2. Initially, in the lag phase, the cell concentration dX
does not increase very much. The length of the lag = j.lX -kdX (Equation 1)
dt
phase depends on the growth history of the inoculum,
the composition of the medium, and the amount of where: X is the biomass concentration at time t; 1-1 is
the specific growth rate (i.e. growth rate per unit
culture used for inoculation. An excessively long lag
phase ties up the fermenter unproductively - hence cell mass); and kd is the specific death rate. During
exponential growth, the specific death rate is neg
the duration of the lag phase should be minimized.
ligible and Equation 1 reduces to Equation 2:
Short lag phases occur when: the composition of the
medium and the environmental conditions in the seed dX = pX (Equation 2)
culture and the production vessel are identical (hence dt
less time is needed for adaptation); the dilution shock For a cell mass concentration X0 at the beginning
is small (i.e. a large amount of inoculum is used); and of the exponential growth (X0 usually equalling the
the cells in the inoculum are in the late exponential concentration of inoculum in the fermenter), and
phase of growth. The lag phase is essentially an adap taking the time at which exponential growth com
tation period in a new environment. The lag phase is mences as zero, Equation 2 can be integrated to
followed by exponential growth, during which the produce Equation 3:
cell mass increases exponentially. Eventually, as the
X
In-= j.lt (Equation 3)
Lag phase Xo
Exponential
growth
Stationary Death Using Equation 3, the biomass doubling time, td, can
phase phase
be derived (Equation 4):
ln2
td =- (Equation 4)
J1
Doubling times typically range over 45-160 min. Bac
teria generally grow faster than yeasts, and yeasts
multiply faster than moulds. The maximum biomass
0 concentration in submerged microbial fermentations
Fermentation time is typically 40-50 kg m-3
Figure 2 Typical growth profile of microorganisms in a sub The specific growth rate J.l depends on the con
merged culture.
centration S of the growth-limiting substrate, until
the concentration is increased to a non-limiting level 02 demand, or the fermentation will be Orbmited.
and ll attains its maximum value llmax The dependence 02 demand is especially difficult to meet in viscous
of the growth rate on substrate concentration typ fermentation broths and in broths containing a large
ically follows Monad kinetics. Thus the specific concentration of Orconsuming cells. As a general
growth rate is given a.s Equation 5: guide, the capability of a fermenter in terms of 02
s (Equation 5)
supply depends on the aeration rate, the agitation
f.1 = f.lmax ks + S intensity and the properties of the culture broth. In
large fermenters, supplying 02 becomes difficult when
where k, is the saturation constant. Numerically, k, is demand exceeds 4-5kgm-3 h- 1
the concentration of the growth-limiting substrate
At concentrations of dissolved 02 below a critical
when the specific growth rate is half its maximum
level, the amount of 02 limits microbial growth. The
value.
critical dissolved 02 level depends on the micro
An excessively high substrate concentration may
organism, the culture temperature and the substrate
also limit growth, for instance by lowering water
activity. Moreover, certain substrates inhibit product being oxidized. The higher the critical dissolved 0 2
formation, and in yet other cases, a fermentation value, the greater the likelihood that 0 2 transfer will
become limiting. Under typical culture conditions,
product may inhibit biomass growth. For example,
fungi such as Penicillium chrysogenum and Asper
ethanol produced in the fermentation of sugar by
gillus oryzae have a critical dissolved 02 value of
yeast can be inhibitory to cells. Multiple lag phases
about 3.2 x 10-4 kgm-3 For bakers' yeast and Esch
(or diauxic growth) are sometimes seen when two or
erichia coli, the critical dissolved Oz values are
more growth-supporting substrates are available. As
6.4 x 10-5 kg m-3 and 12.8 x 10-5 kg m-3 respectively.
the preferentially-utilized substrate is exhausted, the
The aeration of fermentation broths generates
cells enter a lag phase while the biochemical machin
foam. Typically, 20-30% of the fermenter volume
ery needed for metabolizing the second substrate is
must be left empty to accommodate the foam and
developed. Growth then resumes. Details of the kin
allow for gas disengagement. In addition, mechanical
etics of continuous culture, fed-batch fermentation,
'foam breakers' and chemical antifoaming agents are
product formation and more complex phenomena,
commonly used. Typical antifoams are silicone oils,
such as the inhibition of growth by substrates and
vegetable oils and substances based on low-molecular
products, are given in the references listed under
weight polypropylene glycol or polyethylene glycol.
Further Reading.
Emulsified antifoams are more effective, because they
Aeration and Oxygen Demand disperse better in the fermenter. Antifoams are added
in response to signals from a foam sensor. The exces
Submerged cultures are most commonly aerated by
sive use of antifoams may interfere with some down
bubbling with sterile air. Typically, in small fer
stream separations, such as membrane filtrations -
menters, the maximum aeration rate does not exceed hydrophobic silicone antifoams are particularly
1 volume of air per unit volume of culture broth. In
troublesome.
large bubble columns and stirred vessels, the
maximum superficial aeration velocity tends to be Heat Generation and Removal
< 0.1 m s-1 Superficial aeration velocity is the volume
All fermentations generate heat. In submerged cul
flow rate of air divided by the cross-sectional area
tures, typically 3-15kWm_, comes from mictoolat
of fermenter. Significantly higher aeration rates are
activity. In addition, mechanical agitation of the broth
achievable in airlift fermenters. In these, aeration gas
produces up to 15 kW m- 3 Consequently, a fermenter
is forced through perforated plates, perforated pipes
or single-hole spargers located near the bottom of must be cooled to prevent a rise in temperature and
damage to the culture. Heat removal tends to be
the fermenter. Because 0 2 is only slightly soluble in
difficult, because typically the temperature of the
aqueous culture broths, even a short interruption of
cooling water is only a few degrees lower than that
aeration results in the available 02 becoming quickly
of the fermentation broth. Therefore industrial fer
exhausted, causing irreversible damage to the culture. mentations are commonly limited by their heat-trans
Thus uninterrupted aeration is necessary. Prior to use fer capability. The ability to remove heat depends
for aeration, any suspended particles, microorganisms
on: the surface area available for heat exchange; the
and spores in the gas are removed by filtering through
temperature difference between the broth and the
microporous membrane filters.
cooling water; the properties of the broth and the
The 02 requirements of a fermentation depend on
coolant; and the turbulence in these fluids. The geom
the microbial species, the concentration of cells, and
etry of the fermenter determines the surface area that
the type of substrate. 0 2 supply must at least equal
can be provided for heat exchange. Heat generation
FERMENTATION {INDUSTRIAL}/Basic Considerations 667
due to metabolism depends on the rate of 02 con tubular photobioreactors, bubble columns and airlift
sumption, and heat removal in large vessels becomes systems. Tubular bioreactors use a 'solar receiver',
difficult as the rate of 02 consumption approaches consisting of either a continuous tube looped into
5 kgm-3 h- 1 several U-shapes to fit a compact area, or several
A fermenter must provide for heat transfer during parallel tubes connected to common headers at either
sterilization and subsequent cooling, as well as remov end. The continuous looped-tube arrangement is less
ing metabolic heat. Liquid medium, or a slurry, for a adaptable, because the length of the tube cannot
batch fermentation may be sterilized using batch or exceed a certain value: photosynthetically-produced
continuous processes. In batch processes, the medium 02 builds up along the tube, and high levels of dis
or some of its components and the fermenter itself solved 02 inhibit photosynthesis. The parallel-tube
are commonly sterilized together in a single step, by arrangement can be readily scaled up by increasing
heating the medium inside the fermenter. Steam may the number of tubes. Typically, the tubes are 0.05-
be injected directly into the medium, or heating may 0.08 min diameter and the continuous-run length of
take place through the fermenter wall. any tube does not exceed 50 m. However, greater
Heating to high temperatures (typically 121oq lengths may be feasible, depending on the flow vel
during sterilization often leads to undesirable reac ocity in the tube. The tubular solar receivers may be
tions between components of the medium. Such reac mounted horizontally, or horizontal tubes may be
tions reduce the yield, by destroying nutrients or by stacked in a ladder configuration, forming the rungs
generating compounds which inhibit growth. This of the ladder. The latter arrangement reduces the area
thermal damage can be prevented or reduced by ster of land required.
ilizing only certain components of the medium in The culture is circulated through the tubes by an
the fermenter and adding other, separately-sterilized airlift pump or other suitable low-shear mechanism.
components, later. Sugars and nitrogen-containing The maximum flow rate is limited by the tolerance of
components are often sterilized separately. Dissolved the algae to hydrodynamic stress. The flow velocity is
nutrients that are especially susceptible to thermal usually 0.3-0.5 m s- 1 The tube diameter is limited by
degradation may be sterilized by passage through the need to achieve adequate penetration of light. This
hydrophilic polymer filters, which retain particles of declines as the cell concentration increases, due to
0.45J.!m or more. Even finer filters (e.g. retaining self-shading. Closed, temperature-controlled outdoor
particles of 0.2Jlm) are also available. tubular systems attain significantly higher prod
The heating and cooling of a large fermentation uctivity than open channels. The protein content of
batch takes time, and ties up a fermenter unpro the algal biomass, and the adequacy of the devel
ductively. In addition, the longer a medium remains opment of colour (chlorophyll) affect the acceptability
at a high temperature, the greater the thermal deg of the product.
radation or loss of nutrients. Therefore, continuous Among other types of culture system, airlift devices
sterilization of the culture medium en route to a pre tend to perform better than bubble columns because
sterilized fermenter is preferable, even for batch fer only part of the airlift system is aerated and hence the
mentations. Continuous sterilization is rapid and it penetration of light is less affected by air bubbles.
limits nutrient loss - however, the initial capital Conventional external-loop airlift devices may not be
expense is greater, because a separate sterilizer is suitable because of the relatively high hydrodynamic
necessary. shear rates they generate. However, concentric-tube
Photosynthetic Microorganisms airlift devices, with gas forced into the draft tube
(zone of poor light penetration), are likely to perform
Photosynthetic cultures of microalgae and cyano well. Also, split-cylinder types of airlift system may
bacteria require light and C02 as nutrients. Micro be suitable. However, the volume of the aerated zone
algae such as Chiarella and the cyanobacterium in any airlift device for microalgal culture should not
Spirulina are produced commercially as health foods exceed approximately 40% of the total volume of the
in Asia. Algae are also cultivated as aquaculture feeds circulating zones. This way the light blocking effect
for shellfish. of bubbles remains confined to a small zone.
Typically, open ponds or shallow channels are used
Submerged-culture Fermenters
for the outdoor photosynthetic culture of microalgae.
Culture may be limited by the availability of light, Types The major types of submerged-culture bio
but under intense sunlight, photoinhibition limits reactor are:
productivity. Temperature variations also affect stirred-tank fermenter
performance. bubble column
More controlled production is achieved in outdoor airlift fermenter
(A)
(B)
668 FERMENTATION (INDUSTRIAL)/Basic Considerations
(C)
0 0 0
0 0
0 0
0 0
Air
t------t------>-r-Liquid
overflow
Packing
0 0 0
Riser Downcomer
Recycle
0 0
(F) T
Product
Figure 3 Types of submerged-culture fermenter. (A) Stirred-tank fermenter. (B) Bubble column. (C) Internal-loop airlift fermenter.
(D) External-loop airlift fermenter. (E) Fluidized-bed fermenter. (F) Trickle-bed fermenter.
(C)
(A) (B)
(F)
(D) (E)
Gambar 4 Impellers untuk pengaduk tangka fermenter. (A) Rushton disc turbine (radial flow). (B) Marine propeller (axial flow). (C)
Lightnin' hydrofoil (axial flow). (D) Prochem hydrofoil (axial flow). (E) lntermig (axial flow). (F) Chemineer hydrofoil (axial flow).
Mirip dengan kolom gelembung dengan penampang preferred, but the less expensive Type 304L (or 304)
diperluas bagian atas. C a i r a n d i r e s i r k u l a s i may be used in less corrosive situations. Fermenters
t e r u s d i p o m p a k e v e s s e l b a g i a n , pada are typically designed with clean-in-place capability.
kecepatan yang cukup untuk fluidize padatan atau A typical submerged-culture vessel has the features
menjaga mereka dalam suspensi. Fermentor ini shown in Figure 5. Sight glasses in the side and top of
memerlukan pompa eksternal. Bagian atas diperluas the vessel allow for easy viewing. The top sight glass
untuk memperlambat kecepatan dari aliran bagian atas, can be cleaned during fermentation, using a short-dur
sehingga padatan tidak keluar dari bioreaktor. ation spray of sterile water derived from condensed
steam. An external lamp is provided, to light the vessel
Trickle-bed Permenter (Lihat Gambar. 3(F).) B e j a n a
through the sight glass or a separate window.The vessel
ini terdiri dari silinder dikemas dengan
has ports for sensors of pH, temperature and dissolved
d u k u n g a n m a t e r i (e.g. woodchips, batu, struktur
plastik). Sup port memiliki ruang terbuka yang luas, 02 A steam-sterilizable sampling valve is provided.
untuk aliran cairan dan gas dan Connections for the introduction of acid and alkali (for
pertumbuhan mikroorganisme pada pH control), antifoam agents, substrate and inoculum
d u k u n g a n y a n g s o l i d .Sebuah nutrisi cair are located above the liquid level in the bioreactor
disemprotkan ke bagian atas bahan pendukung, dan vessel. Additional ports on the top support a foam
menetes ke bagian bawah, udara dapat mengalir ke sensing electrode, a pressure sensor and sometimes
bagian atas, berlawanan dengan aliran cairan. Fermentor ini other instruments. Filter-sterilized gas for aeration is
digunakan dalam produksi cuka, serta proses-proses lain. supplied through a submerged sparger.Sometimes C02
Mereka cocok untuk cairan dengan viskositas rendah or ammonia may be added to the aeration gas, for pH
dan beberapa padatan tersuspensi. control.
A harvest valve is located at the lowest point on the
Design Irrespective of their configuration, industrial fermenter. A mechanical agitator, entering from either
bioreactors for sterile operations are designed as pres the top or the bottom, may be used. The agitator shaft
sure vessels, capable of being sterilized in situ with supports one or more impellers, of various designs
saturated steam at a minimum guage pressure of (Fig. 4). A high-speed mechanical foam breaker may
0.11 MPa. Typically, the bioreactor is designed for a be provided at the top of the vessel, and waste gas
maximum allowable working pressure of 0.28- may exit through the foam breaker. Commonly, the
0.31 MPa (guage) and a temperature of 150-180C. exhaust gas line also has a heat exchanger, to condense
The vessels are designed to withstand a full vacuum. and return water in the gas to the fermenter. The top
Modern commercial fermenters are predominantly
made of stainless steel. Type 316L stainless steel is
670 FERMENTATION (INDUSTRIAL}/Basic Considerations
Exhaust- -Conditioned
air
-Exhaust
-+-Air
Motor
Figure 10 Rotary drum fermenter.
(Fig. 9). A common central shaft rotates the discs. Figure 11 Agitated-tank fermenter.
Inoculated substrate is introduced into the upper
chamber, and slowly moved to the transfer screw.
The upper screw transfers the partly fermented solids mounted in cylindrical or rectangular tanks, to agitate
through a mixer to the lower chamber, where further the fermented substrate (Fig. 11). Sometimes, the
fermentation occurs. The fermented substrate is har screws extend into the tank from mobile trolleys,
vested using the lower transfer screw. Both chambers that ride on horizontal rails located above the tank.
are aerated with humidified, temperature-controlled Another stirred-tank configuration is the paddle fer
air. Rotary disc fermenters are used in large-scale koji
menter. This is similar to the rotary drum device, but
production in Japan. the drum is stationary and periodic mixing is achieved
by motor-driven paddles supported on a concentric
Rotary Drum Permenter The cylindrical drum of
shaft.
the rotary drum fermenter is supported on rollers,
and rotated at 1-5 r.p.m. around the long axis (Fig.
10). Rotation may be intermittent, and the speed may
vary with the fermentation stage. Straight or curved
baffles inside the drum aid in the tumbling of the Continuous Screw Permenter In this type of
substrate, hence improving aeration and temperature fermenter, sterilized, cooled and inoculated sub
control. Sometimes the drum can be inclined, causing strate is fed in through the inlet of the non-aerated
the substrate to move from the higher inlet end to the chamber (Fig. 12). The solids are moved towards
lower outlet during rotation. Aeration occurs through the harvest port by the screw, and the speed of
coaxial inlet and exhaust nozzles. rotation and the length of the screw control the
fermentation time. This type of fermenter is suit
Agitated-tank Permenter In this type of fermenter, able for continuous anaerobic or microaerophilic
either one or more helical-screw agitators are fermentations.
Sterile substrate
and inoculum Further Reading
Chisti Y (1989) Airlift Bioreactors. London: Elsevier
Applied Science Publishers.
Chisti Y (1992) Build better industrial bioreactors. Chem.
Eng. Prog. 88(1): 55-58.
Chisti Y (1992) Assure bioreactor sterility. Chern. Eng.
Prog. 88(9): 80-85.
Chisti Y (1998) Biosafety. In: Subramanian G (ed_) Rio
Fermented
separation and Bioprocessing. Vol. 2, p. 379. New York:
product Wiley-VCH.
Chisti Y (1999) Solid substrate fermentations, enzyme pro
Figure 12 Continuous screw fermenter. duction, food enrichment. In: Flickinger MC and Drew
SW (eds) Encyclopedia of Bioprocess Technology. Vol.
5, p. 2446. New York: John Wiley.
Chisti Y and Moo-Young M (1991) Fermentation tech
Safe Fermentation Practice
nology, bioprocessing, scale-up and manufacture. In:
The microorganisms used in certain industrial fer Moses V and Cape RE (eds) Biotechnology: The Science
mentations are potentially harmful. Certain strains and the Business.P. 167. New York: Harwood Academic
have caused fatal infections in immunocompromised Publishers.
individuals, and rare cases of fatal disease in pre Chisti Y and Moo-Young M (1994) Clean-in-place systems
for industrial bioreactors: Design, validation and oper
viously healthy adults have also been reported. Micro
ation. ]. Ind. Microbial. 13: 201-207.
bial spores and fermentation products, as well as Crueger Wand Crueger A (1990) Biotechnology: A Text
microbes, have been implicated in occupational dis book of Industrial Microbiology, 2nd edn. Madison:
eases. Most physiologically active fermentation prod Science Tech Publishers.
ucts are potentially disruptive to health, and certain Doran PM (1995) Bioprocess Engineering Principles.
products are highly toxic. The product spectrum of a London: Academic Press.
given microorganism often depends on the fer Hambleton P, Melling J and Salusbury IT (eds) (1994)
Biosafety in Industrial Biotechnology. London:
mentation conditions. Under certain environmental
Chapman & Hall.
conditions, some organisms, e.g. Aspergillus flavus Steinkraus KH (ed.) (1989) Industrialization of Indigenous
and A. oryzae, are known to produce lethal toxins, Fermented Foods. New York: Marcel Dekker.
and specific strains of the blue-veined cheese mould Wang DIC, Cooney CL, Demain AL et al (1979) Fer
Penicillium roqueforti also produce mycotoxins under mentation and Enzyme Technology. New York: John
narrowly defined environmental conditions. Poor Wiley.
operational practice and failings in process and plant Ward OP (1989) Fermentation Biotechnology. Stony Strat
design can increase the risks. The safety aspects of ford: Open University Press.
industrial fermentations are considered in some of
the literature cited under Further Reading. Consumer Media for Industrial
safety, product quality and the cleanliness of a fer
mentation product should be ensured by compliance Fermentations
with Good Manufacturing Practices (GMP). Graeme M Walker, School of Molecular and Life
Sciences, University of Abertay Dundee, UK