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Second, the changes in the amino acid supply occurred via the stringent response. While the
authors did not rule out either explanation, this study demonstrates that two populations
can readily and quickly evolve to form a successful consortium.
APPLICATIONS OF SYNTHETIC CONSORTIA IN INDUSTRIAL
PROCESSES AND MEDICINE
Increasing attention is being paid to the industrial and medical applications that microbial
consortia may offer. To date, synthetic circuits with medical applications have been engineered
in single populations, and include bacteria that target cancer cells (e.g. 44 ), viruses that destroy
biofilms (e.g. 45 ), bacteria that prevent infection, 46 and circuits designed to prevent the spread
of vector-borne pathogens (e.g. 47 ). While consortia with direct medical applications have yet
to be created, such consortia may offer a more robust mechanism that is tolerant to a wide
variety of environments and is stable for longer periods of time as compared to their single
population counterparts. As such, it is conceivable that consortia have future roles in the
production of pharmaceuticals, drug delivery, and the control of infectious diseases.
As compared to medical applications, more progress has been made in engineering
consortia for industrial processes. The benefit of dividing tasks with a high metabolic
burden between two populations has been readily utilized in the fermentation of sugars
towards the creation of biofuels. 13,48 While the majority of biofuel production to date uses
expensive crops such as sugar cane, there is a growing desire to use lignocellulosic materials
from less-expensive crops for the production of biofuels. Hydrolysis of lignocellulosic
materials yields two sugars, glucose and xylose, both of which require efficient fermentation
in the biofuels process. 49 However, E. coli preferentially ferments glucose, followed by
xylose, thus making concurrent degradation of both sugars impossible. However, Eiteman
et al. 48 engineered two strains of E. coli which preferentially degrade glucose or xylose.
In one strain, the authors deleted glk (a cytoplasmic glucokinase), ptsG (a component of
glucose import), and manZ (required for mannose import) genes, thus inhibiting the strain
from degrading glucose. In a second strain, the authors deleted xylA (catalyzes the first step
in xylose catabolism), thus inhibiting the strain from degrading xylose. Coculture of these
populations resulted in efficient and simultaneous fermentation of both sugars.
256
FUTURE CHALLENGES
The design and engineering of synthetic consortia face many of the same challenges that
synthetic biology using single populations does. While current research is forming a solid
foundation describing how robust and predictable behaviors may be rationally engineered,
the field must now move towards more application-based circuits. However, there are
several challenges that need to be addressed. While it is often cited that synthetic systems
are predictable, interactions with the host physiology may have unintended and surprising
effects on a desired behavior (e.g. 8 ). While consortia are often more stable than single
populations, they are still subject to
mutations, which may lead to loss of
circuit function and destabilization of the consortium. As such, a consortium may perform
a desired behavior for a discrete length of time before the consortium must be replaced.
Finally, there are currently many ethical issues surrounding the use of synthetic biology, 50
which must be addressed by both scientists and lawmakers alike.
circuit blind
'
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References
1. Gardner TS, Cantor CR, Collins JJ. Construction of a genetic toggle switch in Escherichia coli . Nature . 2000;403
(6767):339
342.
2. Kobayashi H, Kærn M, Araki M, et al. Programmable cells: interfacing natural and engineered gene networks.
Proc Natl Acad Sci USA . 2004;101(22):8414
8419.
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