Biology Reference
In-Depth Information
metabolites to generate useful products such as biofuels or biomaterials. Metabolic
interactions, inhibitory or beneficial, across the microbial networks must be carefully
engineered.
6,27,68,69
For example, byproduct inhibition occurs when growth or productivity
of a strain is impaired by the compound it produces.
70
For example,
Actinotalea fermentan
can efficiently process cellobiose feedstocks (switchgrass, corn stover, bagasse, etc.) into
acetate, but its growth rate is significantly impaired by even moderate levels of acetate. Bayer
et al. demonstrate that acetate byproduct inhibition of
A. fermentan
can be removed by
addition of an engineered
Saccharomyces cerevisiae
strain which utilizes acetate for growth.
71
The yeast is then engineered to produce methyl halides, which is a useful biofuel precursor.
A 12 000-fold improvement was achieved using this approach compared to levels from
single-culture bioreactors.
Synthetic consortia additionally enable membrane-bound enzyme complexes, such as those
for engineering H
2
production in
E. coli
, to be maximally utilized.
72
Integration of strain
into an engineered consortium through metabolic cross-feeding is a more modular
approach that allows optimization of partitioned functions such as protein engineering of
membrane-bound complexes. Similarly, membrane-associated extracellular mini-
cellulosomes that spatially colocalize can improve reaction rate and efficiency to improve
performance of synthetic consortia.
73
A four-member cellulosome-generating yeast consortia
was recently demonstrated for ethanol production, reaching 87% of theoretical yield
a
three-fold increase over a monoculture strain that expressed all four enzymes.
74
Thus,
utilizing synthetic consortia for modular and programmable biosynthesis of useful
compounds remains very promising.
FUTURE PROSPECTS FOR SYNTHETIC ECOSYSTEMS
Here we have discussed many of the interesting applications that have recently emerged
from the area of synthetic microbial ecosystems. In most cases, these represent the low
hanging fruits of this area
322
systems involving only a handful of strains with relatively
simple interactions. However, these advances can be further extended using new tools in
synthetic biology, mathematical modeling, and molecular biotechnology. Future
developments in this area have the potential to transform fields of medicine, bioproduction,
bioprocessing, and environmental engineering. Precise manipulation and multiplexed
control of community composition, capabilities, and dynamics will generate a suite of
reconfigurable cellular modules that can meet the myriad of health and environmental
challenges that we face in the near future. Additional insights that reveal how these
engineered systems respond to evolutionary pressures in natural environments will guide
their proper use in socially responsible ways.
Acknowledgments
H.H.W. acknowledges funding from the National Institutes of Health Director's Early Independence Award (Grant
1DP5OD009172-01). M.T.M. is supported through funding from the Department of Energy Genomes to Life Center
(Grant DE-FG02-02ER63445).
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3. Basu S, et al. A synthetic multicellular system for programmed pattern formation.
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4. Schink B. Synergistic interactions in the microbial world.
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