Biology Reference
In-Depth Information
community. The sequestration of undesirable compounds or pollutants can be augmented
by reducing inhibition of cell growth that results from accumulation of inhibitory
intermediates. For example, Li et al. demonstrated that an engineered
E. coli
and
Ochrobactrum
consortia can enhance the degradation of methyl parathion (MP), an
insecticide and toxin, through removal of the growth-inhibitory intermediate p-nitrophenol
(PNP), resulting in 98% MP removal.
58
Degradation profiles can further be improved using
engineered microbes that supplement a consortium with limiting metabolites, such as
biotin, thiamine, cobalamine, and siderophores that help facilitate growth and
bioconversion. Examples of these communities of cyanobacteria or microalgae with bacteria
have been documented to greatly improve degradation of hydrocarbons in oil spills.
59
Microbial communities play a significant role in digestion and metabolism of foods in the
mammalian gut, and its dysfunction may lead to diseases of maldigestion.
60
Perturbation of
synthetic communities of gut microbes in gnotobiotic mice using altered diets demonstrated
that digestive capabilities may be a viable avenue of forward engineering through synthetic
biology.
61
For example, gut communities that additionally carry methanotrophic Archaea
can lead to an overall increase in microbial metabolism though removal of inhibitory levels
of hydrogen that are otherwise generated. This has the direct effect of increased degradation
of nutrient into absorbable nutrition, leading to elevated nutritional uptake by the host
which when in excess can cause obesity.
62
Engineering and altering the degradation capacity
of gut-associated microbial communities will likely be an important avenue to develop for
synthetic microbial ecosystems.
Biosynthesis
Synthesis of new compounds, or existing ones using safer and better approaches, is critically
needed
a task well-suited for engineered consortia. More efficient use of otherwise waste
feedstocks as input materials into fermentation bioreactors is a highly desirable objective.
Many of these materials, such as cellulosic biomass, are complex feedstocks that are not
well-suited for current bioproduction pipelines. Use of engineered communities
63
presents a
better solution than current monoculture production approaches, as excretion of different
cellulases from different strains can improve degradation of complex cellulose polymers
into smaller monomers. Additionally, cells that optimally excrete these cellulases may not
be well-suited for bioproduction due to inherent metabolic costs. Shin et al. demonstrated
the advantage of using a synthetic consortium with a divided labor structure for ethanol
production from hemicellulosic feedstock.
64
Two
E. coli
strains were cocultured; one
genetically optimized for cellulase production and excretion, and the other for utilization of
the digested substrate for conversion to ethanol. Ethanol production reached 70% of
theoretical yield in the coculture compared to 26
321
28% with single strains. The use of
orthologous secretion systems can further improve specificity of secretion, and improve
efficiency of secretion by limiting saturation through dividing different processes across
multiple strains.
65
Medical applications of engineered microbes include in situ biosynthesis and excretion of
therapeutic compounds such as cytokines and immunomodulating proteins at the site of
injury.
66
Introduction of nonpathogenic engineered
Lactococcus lactis
that can produce
interleukin 10 in the mouse gut ameliorated autoinflammatory diseases such as colitis,
Crohn
s, and inflammatory bowel disease.
67
Improving the engineering of complex
microbial ecosystems to stably maintain desired strains in challenging environments such as
the human gastrointestinal tract will increase the longevity and effectiveness of these
therapies.
'
Microbial consortia with modular architecture may enable more programmable
reconfiguration of biosynthesis objectives and optimization conditions. Degradation strains
and production strains can be combined modularly using shared common intermediate
