COBIOT-445; NO OF PAGES 6
Integrating ecology into biotechnology
Katherine D McMahon1, Hector Garcia Martin2 and Philip Hugenholtz2
New high-throughput culture-independent molecular tools
are allowing the scientific community to characterize and
understand the microbial communities underpinning
environmental biotechnology processes in unprecedented
ways. By creatively leveraging these new data sources,
microbial ecology has the potential to transition from a purely
descriptive to a predictive framework, in which ecological
principles are integrated and exploited to engineer systems
that are biologically optimized for the desired goal. But to
achieve this goal, ecology, engineering and microbiology
curricula need to be changed from the very root to better
promote interdisciplinarity.
Addresses
1
Department of Civil and Environmental Engineering, University of
Wisconsin-Madison, 1415 Engineering Drive, Madison, WI, USA
2
Microbial Ecology Program, DOE Joint Genome Institute,
2800 Mitchell Drive, Walnut Creek, CA, USA
Corresponding author: McMahon, Katherine D
(tmcmahon@engr.wisc.edu)
Current Opinion in Biotechnology 2007, 18:1–6
This review comes from a themed issue on
Environmental biotechnology
Edited by Eliora Z Ron and Phillip Hugenholtz
0958-1669/$ – see front matter
# 2007 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.copbio.2007.04.007
Introduction
Ecology is the study of the distribution and abundance of
organisms and their biotic and abiotic interactions in an
environmental setting. Biotechnological processes often
rely on microbial organisms contained within an engin-
eered environment designed to allow some level of
operator control. All too often, however, such processes
overlook or ignore the microbial communities that under-
pin the process. This has not necessarily been due to a lack
of interest in the underlying communities, but primarily
because of a lack of tools with which to dissect and monitor
microbial organisms in a cost-effective and timely fashion.
To date, efforts to describe microbial communities of
biotechnological relevance have been largely descriptive.
However, a plethora of new high-throughput culture-
independent molecular tools [1] hold the promise of
turning microbial ecology into a quantitative predictive
science. Once the discipline becomes predictive, it can
then be used to improve biotechnological processes in a
directed manner, in much the same way that advances in
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aerodynamics, combustion and electronics translated into
more efficient and cheaper automobiles. But first, environ-
mental biotechnologists must survive the indigestion pro-
duced by a data overload from the new tools, and learn how
to best use these data to create a quantitative predictive
framework. In this review, we will mainly use wastewater
treatment processes to illustrate the use of ecological
principles in understanding biotechnological processes.
From tools to principles
Many authors before us have remarked on the revolution-
ary impact that molecular tools have had on the disciplines
of microbial ecology and environmental biotechnology
over the past two decades [2,3,4,5]. As we continue to
move beyond the cataloging of 16S rRNA genes and
begin to catalog whole (meta)genomes, (meta)transcrip-
tomes, (meta)proteomes, and ultimately (meta)metabo-
lomes [1,6,7], the need to work within a framework
designed to integrate data at a previously unimaginable
scale is becoming ever greater. We will need to turn to the
disciplines of ecology and ecosystem science for guidance.
Here we emphasize the need to go beyond descriptive
science and apply theoretical ecology to understand,
model, and manage environmental biotechnology sys-
tems. The basic principles of ecology developed during
a century of study focused on how macroscale organisms
interact with their environment and fellow community
members should be mined by environmental biotechnol-
ogists for useful conceptual frameworks.
Environmental biotechnology systems tend to be engi-
neered to select for a few high-performing functional
groups that may or may not be represented by a single
coherent phylogenetic group. Examples include nitrifiers
in activated sludge [8], reductive dechlorinators in con-
taminated groundwater [9] or methanogens in anaerobic
digesters [10]. Engineers and microbial ecologists alike
have been preoccupied by the search for ‘super bugs’
capable of carrying out these kinds of crucial processes
quickly, reliably, and predictably. At first glance this
approach seems quite reasonable: enrich for the best
organism available to get the job done for the least cost.
However, when addressed within an ecological frame-
work, the objective of designing and operating stable and
resilient high-performing systems could be met in strik-
ingly different ways.
A disturbing mind-set
Perhaps the most widely appreciated concept borrowed
from ecologists by environmental biotechnologists is the
proposed relationship between biodiversity and system
Current Opinion in Biotechnology 2007, 18:1–6
COBIOT-445; NO OF PAGES 6
2 Environmental biotechnology
stability [3,5,11]. The latter can be characterized by
measures of resistance, resilience, and scale of temporal
variability. Although ecologists still debate whether
positive correlations between diversity and stability are
universal (and therefore useful for predictive purposes)
[12–15], much theoretical and experimental work has been
done to explore the processes that could be generating this
relationship. The uncoupling of stability in ecosystem
function and community composition is of particular in-
terest as environmental biotechnologists seek to under-
stand the significance of observed community dynamics in
the face of stable process performance [5,16].
One of the most puzzling observations made by ecologists
was elegantly articulated by Hutchinson in the classic
‘paradox of the plankton’ [17]. Simply put, why do we
observe multiple species with over-lapping niches (i.e.
functions) co-existing in an ecosystem, when the principles
of competitive exclusion dictate that they should not? A
popular answer to this question points to the influence of
habitat heterogeneity in both time and space, which is the
foundation of the Intermediate Disturbance Hypothesis
[18]. This conceptual framework integrates observed pat-
terns of community succession and spatial heterogeneity.
Disturbances occurring at different scales and frequencies
create patches (either in space or time) that harbor com-
munities in varying stages of succession towards a climax.
Most ecosystems we observe are not yet at equilibrium,
which would be characterized by competitive exclusion by
the fittest species. Thus, any community under the influ-
ence of periodic disturbances acting externally to the
system would not be expected to be at equilibrium. Com-
munity succession was recently linked to the development
of stable process performance in a circulation flush toilet
[19]. Convergent succession appeared to occur in a five-
compartment anaerobic migrating blanket reactor per-
turbed by sulfate [20] and in activated sludge systems
fed with non-ionic surfactants [21].
Indeed, environmental biotechnologists must consider the
concept of disturbance from several perspectives. First,
variability in abiotic system components is unavoidable: for
example, wastewater treatment influents are extremely
heterogeneous in time. If ecosystem function (process
performance) is maintained by functional redundancy in
the face of disturbance, then our engineering objective
should be to maximize diversity. An activated sludge
system operated to remove surfactants performed better
and was more resistant to invasion by competitors when the
communities were more diverse [22]. On the other hand,
engineered disturbances can be used to control community
assembly [5,16]. Methanogenic digesters were found to
recover more quickly from organic overload conditions
when their communities had been subjected to previous
perturbations [10]. Competition between acetoclastic
methanogen species with different kinetic characteristics
could be manipulated using a defined digester feeding
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Please cite this article in press as: McMahon KD, et al., Integrating ecology into biotechnology, Curr Opin Biotechnol (2007), doi:10.1016/j.copbio.2007.04.007
strategy [23]. Fluctuating performance and community
dynamics were correlated in denitrifying bioreactors, and
process instability was induced by altering nitrate loadings
[24]. Pulsed nutrient dynamics provided to activated
sludge organisms generated community functions that
were different depending on the pulse regime [25]. Inter-
estingly, community composition was more distinct across
systems than could be explained by the different pulse
regimes explored, suggesting that stochastic inter-specific
interactions played a major role in structuring the bacterial
assemblages. This observation hints at the need to consider
principles of non-linear dynamics and complexity theory,
particularly in the absence of external abiotic disturbances
(see also below) [26]. Future challenges include the need
to determine what type of disturbance regimes will satisfy
our engineering goal of process stability. These may be
very process specific.
Community assembly: from pattern to
process
If our design objectives become directed toward maintain-
ing maximal diversity and functional redundancy, how
does this influence our choice of process configuration
and mode of operation? We could turn to neutral models
such as the Unified Theory of Biodiversity and Biogeo-
graphy [27] when considering ways to predict and control
community assembly. This framework, based on the Island
Theory of Biogeography [28], was developed mainly to
explain patterns observed in communities of macroscale
organisms such as plants and birds, although it is based on
general principles applicable even to the microbial world.
It proposes a stochastic model of community assembly that
relies primarily on rates of immigration and extinction, with
biodiversity being ultimately constrained by the area (or
volume) sampled and dispersal limitations. Microbial ecol-
ogists have only recently attempted to search for and des-
cribe such spatial patterns of taxa distribution [29,30].
However, methodological limitations continue to plague
interpretation of such data [31], as does a lack of infor-
mation about dispersal rates and mechanisms. Different
microbial taxa appear to be influenced to varying degrees
by dispersal limitation. For example, narrowly defined
phylogenetic groups of Candidatus Accumulibacter phos-
phatis, a model polyphosphate-accumulating organism in
activated sludge, appear to be globally dispersed [32,33]
(V Kunin et al., unpublished), while populations of Sulfo-
lobus, a thermophilic archaeon found in hot springs, showed
evidence for geographic isolation [34]. Much effort will be
required to understand and quantify dispersal character-
istics for microbial taxa that are important in environmental
biotechnology systems. Still, neutral community assembly
models are appealing because of their simple architecture
and potential for parameterization [35,36].
Other more deterministic approaches to predicting the
outcome of community assembly weigh more heavily
the importance of interspecific competition and niche
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COBIOT-445; NO OF PAGES 6
Integrating ecology into biotechnology McMahon, Martin and Hugenholtz 3
partitioning. Although this framework often seems diame-
trically opposed to the neutral theories of Hubbell [27] and
Bell [37], ecologists have recently argued that neutral
patterns of distribution and abundance are merely an
emergent property [38] of more deterministic processes
that rely on local selection [39,40,41,42–44]. Theoretical
ecologists are themselves still working to develop concep-
tual models to capture the tension between stabilizing
mechanisms (i.e. niches) and fitness equivalence (neutral-
ity and habitat filtering) that is expected to create observed
patterns of community assembly and species-coexistence
[45–47]. The usefulness of this approach has already been
demonstrated for human gut microbial communities [48].
Principles of non-linear dynamics have also been invoked
to explain oscillatory behavior among populations of com-
petitors in the absence of disturbance [26,49]. These and
other related concepts could easily be applied to studies of
environmental biotechnology systems designed to observe
the community dynamics resulting from non-equilibrium
conditions [50–52], and to make predictions about com-
munity development. Microbial ecologists and environ-
mental biotechnologists will only benefit from becoming
and remaining engaged in this effort to further develop
such models.
An additional layer of complexity: trophic
food web interactions
Microbial communities and populations in engineered
systems are also subject to ‘top-down’ control exerted by
predators such as viruses (bacteriophage) and protozoan
bacteriovores (e.g. ciliates and flagellates). However, few
studies have addressed either type of predator–prey
dynamic. It is noteworthy that models designed to predict
process performance, such as the series of Activated
Sludge Models [53], do not include food-web interactions
of any kind, despite the wealth of theoretical information
available from studies of aquatic microbial food webs. In
particular, viral diversity and abundance in environmental
biotechnology systems is expected to exceed that of
prokaryotic and eukaryotic organisms. A survey of phage
in full-scale wastewater treatment plants and over time
in a laboratory-scale reactor using pulse-field gel electro-
phoresis revealed unexpected similarities in the viral
populations across plants, and differential patterns of
persistence and variability in the laboratory-scale reactor
[54]. No clear relationship was observed between phage
and bacterial community dynamics in the laboratory-
scale reactor. Similarly, no conclusive link between abun-
dance of the activated sludge bacterium Microlunatus
phosphovorans and its lytic phage was observed in a
laboratory-scale enhanced biological phosphorus removal
system [55]. Phage-like particles were also found to be
abundant and dynamic in a methanogenic upflow anae-
robic sludge blanket digester [56]. Prokaryotic commu-
nities were not investigated in this study, but the
authors speculate that predator–prey dynamics could
explain previously observed community and performance
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fluctuations in anaerobic bioreactors. Phage therapy has
been proposed as a promising biocontrol strategy to
manage nuisance organisms (e.g. those causing filamen-
tous foaming and bulking) or to improve pathogen inac-
tivation during wastewater treatment [57], although few
studies have explored this application. Clearly, much
remains to be learned about these important drivers of
prokaryotic community composition in engineered sys-
tems. Again, the most promising approach for directly
accessing viral communities is through the use of high-
throughput culture-independent molecular methods [58].
Describe, explain, predict, control
Ecologists have long used models to try to quantitatively
understand ecosystems. The goal of modeling is to inte-
grate all available data to distill the main processes that
drive the system. A good model should then be capable of
predicting the behavior of the system to the required
resolution. In fact, it is fair to say that if you cannot predict
the behavior of the system you do not really understand it.
The challenge before us is to effectively integrate
community-wide high-resolution molecular data into a
quantitative predictive framework. One promising appr-
oach is flux balance analysis (FBA), a widely used method
for metabolic modeling of microorganisms [59,60].
Although other approaches for modeling cellular pro-
cesses have been developed [61–66], their use in gen-
ome-scale simulations is hampered by the requirement
for a large number of parameters and associated compu-
tational complexity. FBA does not require kinetic para-
meters for the reactions involved and can be scaled to deal
with complete genomes. Moreover, FBA has been shown
to provide predictions of growth rates [67], growth of
gene deletion mutants [68,69] and metabolic fluxes [70],
compatible with experimental data in a high number of
cases for Escherichia coli and other species [71,72].
FBA produces results by finding the set of metabolic
fluxes that maximizes a given goal (typically growth rate
[59]) within a set of constraints. The two fundamental
constraints are the reaction stoichiometry for the meta-
bolic network inferred from the metabolic reconstruction
and empirical data on measurable fluxes (e.g. acetate
uptake or growth rate); other constraints, such as gene
regulation, refine this basic model [73]. Presently,
genome-scale FBA has been restricted to single
pure-culture model organisms, such as E. coli. Very
recently, FBA has been successfully applied to a
simple mutualistic co-culture system comprising a sulfate
reducer and methanogen with available genome sequences
[74]. Several ecologically relevant characteristics in-
cluding co-culture cell ratios and metabolic fluxes could
be predicted using the approach. This heralds the begin-
ning of whole genome-based community modeling at the
molecular level. The next step will be to make use of
metagenomic datasets in a similar way.
Current Opinion in Biotechnology 2007, 18:1–6
COBIOT-445; NO OF PAGES 6
4 Environmental biotechnology
Bridging the gap between the disciplines
We have learned much about the links between
community diversity, composition, and process perform-
ance in environmental biotechnology systems by applying
the powerful molecular tools developed by microbiologists.
However, there is still a great need to develop new curri-
cula and concerted research efforts to better integrate the
knowledge and tools of molecular microbiology and engin-
eering [2]. We propose, as have others [3,5,75], that
students and practitioners of environmental biotechnology
should also embrace the principles of Ecology, with a
capital ‘E’. Even microbiologists need more exposure to
ecology and ecosystem science in their undergraduate and
graduate coursework, and as part of continuing professional
development [76]. Many approaches to experimental
design and data analysis (particularly the use of statistics)
that are fundamental to ecology are completely foreign to
microbiologists classically trained in a scientific culture
born of the Delft School [77] and a continued fixation with
microbial pathogens. Indeed, all three disciplines (micro-
biology, engineering and ecology) would benefit from
more conversation and interaction. Ecologists should
recognize engineered processes as valid model ecosystems
that are simplified enough to be tractable, yet still ‘wild’
enough to be relevant [75].
Conclusions
These are exciting times to be working with biological
systems. Microbial ecology as a discipline is on the verge
of maturing beyond the descriptive phase and we can now
begin to explain observed patterns based on processes
that generate them. As is the case with macroscale
ecology, our ultimate goal is to be able to predict the
behavior of microbial populations and communities. This
goal is especially relevant for applications to environmen-
tal biotechnology systems. Engineers hope to take the
science one step further and learn how to manipulate and
control such systems. They would be wise to explore the
fields of ecology, ecosystem science and systems biology
to develop truly innovative approaches to their trade.
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