Biology Reference
In-Depth Information
Methods to engineer microbial communities have thus far relied on natural selection of
desirable traits, which is very limiting.
13
Engineering at this next level will require new
advances in synthetic biology. Integration of coupled metabolism, directed cell
cell
communication, and programmable community structure for real-world applications will
require tools in in silico design, large-scale genome engineering, and high-throughput DNA
synthesis, among other cutting edge techniques. Here, we highlight important recent
developments that have advanced the field of synthetic ecosystems, and outline crucial areas
for future innovations.
TARGETING MICROBIAL COMMUNITIES FOR
FORWARD ENGINEERING
Genomics has significantly advanced our knowledge of microbial communities, enabling us
to have the potential to engineer and control microbes at the genetic level. DNA and RNA
sequencing have allowed us to determine genomic diversity and transcriptomic profiles of
microbial populations in areas such as bioremediation or bioproduction.
14,15
In silico
models of cellular metabolism can be used to assess flow of metabolites through
individual cells, and are now being scaled across communities of cells.
16
20
New
methods in recombineering,
21
oligo-directed genomic modifications,
22
25
and gene
synthesis
26
have revolutionized how we perturb, understand, and improve the
interactions between cellular components through strain engineering. Applying these tools
to mixed consortia will bring further elucidation of population-level phenomena, such as
interspecies metabolic exchange, community stability, and adaptive evolution.
7,27,28
Emerging advances in synthetic ecology require us to control three important features
outlined below (
Fig. 17.1
).
First, engineering ecosystems requires precise understanding and control of metabolism and
metabolic exchange. Engineering metabolism has thus far mainly focused on the
biosynthetic capabilities of individual cells.
29,30
A key challenge is the elucidation of
metabolism at the population level,
31
and the development of techniques to optimally
combine different metabolic pathways together in useful ways.
32
One avenue of pursuit
may be to physiologically link cells together through metabolic exchange using different
metabolite transport systems. By mining metagenomic libraries for transporters,
33
combined
with cytosolic exchange strategies,
34
interactions across a metabolic network of cells can be
exploited.
35,36
Engineering these metabolic interactions provides a means to control the
degree of antagonistic or beneficial relationships between population members. Modifying
metabolic exchange will improve our understanding of how metabolism can be partitioned
across a heterogeneous mixture of cells, and its effects on the dynamics, functionality, and
efficiency of the system.
318
Second, engineering ecosystems requires directed cell
cell communication. Quorum sensing
(QS) molecules, such as acyl-homoserine lactones, enable microbes to communicate with
one another by diffusion through the extracellular space.
37
Intercellular signaling may also
occur via direct cell-to-cell contact through membrane-bound protein complexes such as
the Notch-Delta system
38
and various bacterial intercytosolic transfer systems.
39
Both
types of signal exact transcriptional responses that affect various cooperative
processes.
40,41
While synthetic gene circuits have been constructed to exploit QS
modules,
3,42,43
more sophisticated circuits need to be developed to produce complex
population behaviors.
Third, engineering ecosystems requires formation of defined spatial structure. Natural
biofilms are a source of inspiration for spatially organizing microbial populations as an
engineering objective.
44
These structures can define intercellular interactions and improve
robustness of the consortia to environmental insults such as antibiotics and predation.
45
