Solid-state fermentation are there any biotechnological
advantages?
Udo Holker1 and Jurgen Lenz2
Solid-state fermentation (SSF) has developed in eastern
countries over many centuries, and has enjoyed broad
application in these regions to date. By contrast, in western
countries the technique had to compete with classical
submerged fermentation and, because of the increasing
pressure of rationalisation and standardisation, it has been
widely superseded by classical submerged fermentation since
the 1940s. This is mainly because of problems in engineering
that appear when scaling up this technique. However, there are
several advantages of SSF, for example high productivities,
extended stability of products and low production costs, which
say much about such an intensive biotechnological application.
With increasing progress and application of rational methods in
engineering, SSF will achieve higher levels in standardisation
and reproducibility in the future. This can make SSF the
preferred technique for special fields of application such as the
production of enzymes and food.
Addresses
1
Institute of Cellular and Molecular Botany, University of Bonn,
Kirschallee 1, 53115 Bonn, Germany
2
Bioreact GmbH, Mulheimer Str. 26, 53840 Troisdorf, Germany
Corresponding author: Holker, Udo (u.hoelker@uni-bonn.de)
Current Opinion in Microbiology 2005, 8:301306
This review comes from a themed issue on
Ecology and industrial microbiology
Edited by Sergio Sanchez and Betty Olson
Available online 5th May 2005
1369-5274/$ see front matter
# 2005 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.mib.2005.04.006
Introduction
The term solid-state fermentation (SSF) denotes cultiva-
tion of microorganisms on solid, moist substrates in the
absence of a free aqueous phase; that is, at average water
activities (defined as the relative humidity of the gaseous
phase in equilibrium with the moist solid) significantly
below 1 [1]. In a broader definition, SSF can be seen as
including processes during which microorganisms are
cultivated in the presence of a liquid phase at maximal
substrate concentrations [2] or on inert carriers [3].
To assess the possible advantages of the biotechnological
uses of SSF relative to those of classical submerged
fermentations (SmFs), different aspects of the two,
including historical, biological, ecological and engineer-
www.sciencedirect.com
ing aspects, will first be considered separately, and then
compared from the economical viewpoint.
Historical aspects
When compared with the SSF processes that have long
been established in Asian countries, SSF in western
countries appears to still be in its infancy. SSF is the
state-of-the-art technology that is used in many applica-
tions in the food industry in Asia. For example, SSF is
used in the production of enzyme-rich Koji (which is
made of rice and uses Aspergillus oryzae as an enzymatic
starter for different hydrolytic processes), in the sacchar-
ification of rice used for the production of alcoholic
beverages such as sake, in the production of cellulase
(which uses Trichoderma strains), and in the production of
angkak, which is rice that is coloured red by Monascus
purpurea metabolites. In Asia, enzymes and metabolites
are commonly produced on a large scale by SSF processes
that may be thousands of years old. These processes vary
widely depending on locality, and are transmitted as
secret formulas from father to son.
In western countries, SSF had to compete with the
technically easier SmF, which was more strongly devel-
oped from the 1940s onwards because of the necessity to
produce antibiotics on a large scale. Today, SSF has been
nearly completely abandoned because of the pressure of
increasing industrial rationalisation and standardisation.
In the east, by contrast, SSF survived in many areas in the
form of labour-convenient, hand-made processes; how-
ever, some of the traditional SSF processes have also been
further developed to achieve higher industrial rationalisa-
tion through stronger automation.
Biological features
SSF processes simulate the living conditions of many
higher filamentous fungi. Ascomycetes, basidiomycetes
and deuteromycetes developed in terrestrial habitats on
wet substrates. For this reason, SSF is the cultivation
method of choice for instance in cases in which the
biotechnological process is required to include morpho-
logical and metabolic differentiation into substrate-pene-
trating and aerial hyphae, such as in the production of
conidiospores. Hence, SSF is used in the food industry in
the production of conidiospores for the production of
mould cheese (for which conidiospores of Penicillium
roquefortii or P. camemberti are needed) or salami improve-
ment (for which conidiospores of P. nalgiovensis can be
used) and also in the field of production of plant protec-
tion agents (which uses Coniothyrium minitans).
Current Opinion in Microbiology 2005, 8:301306
302 Ecology and industrial microbiology
Higher fungi and their enzymes, spores or metabolites are
well adjusted to growth on solid wet substrates. For
instance, fungal spores produced by SSF show higher
stability, are more resistant to drying and exhibit higher
germination rates for extended periods of time after
freeze-drying than do spores produced by SmF. This
can be attributed to the fact that the conidiospores
produced in SSF have a higher hydrophobicity, as was
demonstrated with Penicillium oxalicum [4], or also pos-
sess, apart from a higher hydrophobicity caused by a
hydrophobin-like protein, a stronger cell wall and a smal-
ler volume (this has been documented with Trichoderma
harzianum [5]).
A direct comparison between the SSF and SmF cultiva-
tion modes of fungi is difficult to make because the two
processes differ. Studies of the production of fungal
enzymes in SSF have repeatedly shown that SSF, in
comparison with SmF, provides higher volumetric pro-
ductivities, is less prone to problems with substrate inhi-
bition and yields enzymes with a higher temperature or
pH stability. Also, the fermentation time may be shorter
and the degradation of the enzymes by undesirable
proteases is minimised [6]. Interesting studies in this
field have explored the physiological differences that
arise during the growth of microbial cells in the two types
of processes. In the well-studied fungus Aspergillus oryzae,
water activity seems to play a decisive role in this context
[7]. This is apparent from the accumulation of glycerol,
erythritol and arabinitol [8], and from the induction of
glucoamylase genes, the promoters of which have been
shown to contain motifs that suggest induction by tem-
perature or water activity [9], under SSF conditions.
Similar results were also obtained in studies of the pro-
duction of secondary metabolites [10]. When grown on
solid substrates, numerous fungi have shown a markedly
altered spectrum of secondary metabolites. As described
in streptomycetes, the production of secondary metabo-
lites often seems to be associated with the formation of
aerial hyphae and the onset of spore production in the
stationary growth phase. Various secondary metabolites
have even been shown to be produced solely during
growth on solid substrates, although the fungi in question
can be readily cultivated in submerged processes. For this
reason, SSF could play an interesting role in the screening
for new metabolites and also in the production of these
metabolites by wild-type fungi.
In the employment of microbial mixed cultures, SSF offers
an option that cannot be achieved by SmF. This makes use
of the fact that, during growth on natural substrates, fungal
consortia secrete a broad spectrum of enzymes [1113].
During co-cultivation of different fungi, some of the indi-
vidual enzyme activities show synergistic increase [14],
whereas others remain unchanged [15]. Filamentous fungi
and yeasts can be broadly applied in processes of simulta-
Current Opinion in Microbiology 2005, 8:301306
neous saccharification and fermentation that can be regu-
lated by the joint action of aerobic and facultative anaerobic
processes via the availability of oxygen. In addition, SSF
offers the possibility to explore and to use interactions
between fungi by properly regulating the water activity as a
selection parameter depending on the different water
demands of the individual co-cultivated fungi. Many
SSF processes used in the food industry make use of mixed
cultures that are important for the flavour of the foods
produced. For example, bamboo sprouts can be processed
by undefined mixed cultures that, during the fermentation
process, produce a variety of metabolites including 29
volatile substances with aroma-active properties [16].
Despite the situation when using filamentous fungi, SSF
has only found restricted applications in processes using
unicellular organisms. SSF has, for instance, been used in
the production of endospores (Bacillus thuringiensis) [17],
secondary metabolites by means of aerial mycelium of
streptomycetes [18] or alcohol by yeast on solid sugar-rich
substrates, which can be conveniently combined with
simultaneous or previous hydrolysis of the polysacchar-
ides by extracellular fungal enzymes. Another example is
the production of organic acids (such as vinegar produc-
tion performed in Asia for thousands of years) or the
traditional fermentation of foods [19] by microbial mixed
cultures that involve yeasts and bacteria.
Ecological features
Ecological (environment-protective) advantages of SSF
reflect the fact that the processes are conducted in the
absence of a free aqueous phase. This results in minimum
water consumption and thus a low production of effluent
water by the process, obviation of the necessity to use
antifoam agents, and the possibility of conducting SSF
processes in certain applications under semi-sterile con-
ditions. Because SSF processes are performed at water
activities below 1, the growth of contaminating bacteria
and yeasts is minimised. This means that, in certain cases,
energy- and instrumentation-demanding sterilisation pro-
cesses can be eliminated.
Another additional environmentally friendly feature of
SSF is that, in many cases, it can use agricultural wastes as
carbon and energy sources. The production of enzymes or
organic acids makes frequent use of plant remnants as
carbon sources and inducers or mediators.
Engineering features
The most serious reasons why SSF has not yet found a
broad use in western countries are engineering problems,
the low amenability of the processes to standardisation
and the limited reproducibility of the results. Scale-up
represents a particular bottleneck because several differ-
ent gradients (temperature, humidity, substrate concen-
tration, and so on), which can arise in the course of the
process, can have an adverse effect especially in static
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 Solid-state fermentation Ho lker and Lenz 303

solid bed processes but also in processes involving sub-
strate agitation, such as those performed in rotating
drums. Inter-relationships among environmental factors
such as oxygen content, moisture level and temperature
contribute to the difficult regulation of these parameters.
The microbial growth under aerobic conditions in the
bioreactor results in a considerable production of heat that
causes fast increase in temperature. This effect, which is
desirable in composting, is often fatal for biotechnological
processes because a large part of the enzymes produced
during the fermentation can be heat-denatured at the end
of the process [20]. In the absence of a free aqueous
phase, the produced heat is difficult to remove, for
example, via the bioreactor double walls. Instead, the
cooling of the process takes place through evaporation.
However, this requires very high aeration rates because
the rising metabolic activity and the associated increased
heat production have to be overcompensated by high
aeration intensity. The water escaping by evaporation
has to be in many cases replenished, and this can lead to
undesirable local increase in water activity during static
processing. In semi-sterile processes, this increased
water activity can in turn have adverse effects by facil-
itating the growth of bacterial contaminants, whereas in
sterile fermentations, it may bring about local insufficient
oxygen supply to the microorganisms. Substrate mixing
may help but it should be noted that many microorgan-
isms respond very sensitively to the shear stress caused
by it. Another factor that is difficult to account for is the
production of metabolic water by aerobic microorgan-
isms, which can cause problems especially in the forma-
tion of conidiospores.
Despite all these problems, the development of rational,
at least partly computer-controlled methods of process
development within the past decade brought advances in
the field, leading to a better understanding of biological
and physical processes that take place during the SSF
(Figure 1), and paving the way to new starting points
for further industrialisation of the process [21]. These

Figure 1

O2
g

g Aerial hyphae

Mycelial mat
l
Substrate surface
s s s
CO2
Substrate pores
NH3 l H2O
Q T l
pH Penetrative hyphae
Acids
Products
Enzymes

Polymers
Monomers
Current Opinion in Microbiology

Schematic of some of the microscale processes that occur during solid-state fermentation (SSF). After sporulation, fungal hyphae develop
into a mycelial mat (black), which spreads over the surface of the particles that comprise the solid substrate (brown). From the mycelial mat, aerial
hyphae protrude into the gaseous space, whereas others penetrate the substrate by growing into liquid-filled pores. At normal moisture levels,
the void spaces between the aerial hyphae are most likely to be filled with gas (g), whereas the void spaces within the mycelial mat and
within the substrate are filled with liquid (l). The metabolic activities shown mainly occur near the substrate surface and within the pores; however,
exposed regions of the mycelium (for instance the aerial hyphae) also show metabolism and there can be a transport of substances from the
penetrative to the aerial hyphae. Hydrolytic enzymes (light blue), which are produced by the mycelium, diffuse to the solid matrix and
catalyse the degradation of macromolecules into smaller units (green). The latter are taken up by the fungus to serve as nutrients. O2 is consumed
and CO2, H20, heat and interesting biochemical products are produced during fermentation. Hence, gradients develop within the biofilm that, for
instance, force O2 to diffuse from the gaseous phase into deeper regions of the biofilm (lilac) and CO2 to diffuse from these regions to the gaseous
phase (red). Heat development (Q; orange) leads to a fast increase in temperature (T), which is a serious problem during SSF. Heat is therefore
removed from the substrate not only via conduction but also by evaporation, which is part of the complex balance of water in the system (dark blue).
Beside evaporation, water balance includes water uptake by the mycelium in the course of growth, water consumption during hydrolysis reactions
and water production through respiration. As another important factor, local pH, might be changed owing to the release of carbon acids and
the exchange of ammonia (grey). The biochemical products of interest (magenta) that are released into the solid matrix and the liquid-filled
spaces during fermentation might absorb to the solid and might have to be extracted for further use at the end of the process. All these and
many other phenomena can strongly influence process performance during SSF.

www.sciencedirect.com Current Opinion in Microbiology 2005, 8:301306

304 Ecology and industrial microbiology
developments include progress in the modelling of micro-
bial growth on solid substrates and energy and mass
transfer in different types of bioreactors [2226,27,
28,29,30], formulation of scale-up rules and recommen-
dations for optimal design and scale-up of industrial
bioreactors [3133], new methods for measuring the
spatial distribution of process parameters, evaluation of
parameters that are difficult to measure on-line such as
humidity and biomass [3436], the use of statistical meth-
ods for parameter optimisation [3742], and the develop-
ment of new strategies for process control in SSF [4345].
Interestingly, the practical development of commercially
employed bioreactors proceeded largely independently of
the results of the above studies. This was in part because
of the difficulties in converting the general statements of
rational studies pertaining to bioreactor and process design
into concrete guidelines for specific applications. The
reason again is the lack of sufficient bodies of process
data needed for validating the mathematical models.
Hence, the commercially employed industrial bioreactors
often still represent empirical developments of traditional
processes, or they are large but technically relatively low-
level facilities restricted correspondingly to non-sterile
and robust processes suitable for manufacture of bulk
products (e.g. bioreactors for Koji fermentation). The
engineering shortcomings are then compensated by high
space and time gains and low production costs so that these
processes can be operated with satisfactory economy.
Although a variety of different SSF bioreactors are avail-
able on the laboratory and pilot scale [46], only some of
these variants have the potential for scale-up to the
industrial level because large-volume operations may give
rise to effects, such as the influence of compaction, which
are not perceptible on a smaller scale.
Economic viewpoint
The described biological and environmental benefits of
SSF can bring direct economical advantages that have
much to say for an intensive biotechnological application
of SSF. For instance, calculation of the costs of production
of crude enzymes by SSF showed that, for example in the
case of cellulase production, the economical efficiency is
higher by a factor of 100 than in the case of SmF [47]. This
striking difference has several reasons. In addition to the
much cheaper growth substrates, the minimised require-
ments for sterility and low requirements for instrumenta-
tion and equipment, this approach can make downstream
processes in the production of enzymes unnecessary. In
general, this holds for those cases when the fermented
substrate can be used directly in a follow-up process such as
the saccarification of renewable raw materials employed in
ensiling, production of bio-ethanol or biogas, in the pulp-
and-paper industry, textiles industry or in the production of
animal fodder supplements. This is usually made possible
thanks to the high concentrations of enzymes in the solid
substrates, which makes further concentrating processes
unnecessary. The enzyme activities that have been mea-
Current Opinion in Microbiology 2005, 8:301306
sured in solid substrates can reach levels common in
commercial enzyme preparation [48].
Conclusion
Yet, despite the multitude of the above advantages, a
broad application of SSF is, at least at present, hard to
envisage. The main obstacles are the low amenability of
the process to regulation, the strongly heterogeneous
fermentation conditions and the ensuing frequently unsa-
tisfactory reproducibility of the results, difficult scale-up,
the often unfeasible biomass determination and compli-
cated product purification by downstream processes
resulting from the use of heterogeneous organic growth
substrates. For these reasons, SSF will never replace or
supersede the established processes for the production of
enzymes and metabolites by bacteria or yeasts that have
for decades been successfully cultivated in submerged
bioreactors and also optimised as heterologous expression
systems. Yet only in special cases, SSF can be applicable
also with unicellular organisms.
A different situation exists in the cultivation of differ-
entiating microorganisms, in which SSF simulates the
natural growth conditions and its biological and environ-
mental advantages can outweigh the engineering pro-
blems. In principle, SSF processes can be economically
operated on a large scale despite their engineering diffi-
culties when the technical demands (for example, in non-
sterile processes or in those that do not require further
expensive product processing) and hence also the pro-
duction costs are low. In these cases, SSF can provide
substantial advantages over SmF.
At any rate, even though further progress in the field of
SSF can be expected to bring improved biomonitoring
and thereby optimisation and higher standardisation of
industrial processes, the future applications of SSF for the
above purposes can be expected to be mainly limited to
those that even today exhibit substantial advantages
above all the production of spores, screening for second-
ary metabolites and enzymes, protein enrichment of
fibre-rich natural materials, degradation and bioconver-
sion of plant material [49], and co-cultivation of several
fungi for the production of enzymes [50] and foods.
References and recommended reading
Papers of particular interest, published within the annual period of
review, have been highlighted as:
 of special interest
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