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Revision as of 11:59, 16 September 2015
PROJECT OVERVIEW
Working together to save the world
The Problem
The quest for sustainability
Fossil
Fuels
Our economy still depends largely on fossil resources. For decades, this has fueled the incredible progress of our world, but not without the massive cost of geopolitical instability and global warming - costs we’re now facing more than ever. With the current consequences of climate change visible around the world and global energy demands that are expected to double in 2050, the quest for clean, renewable energy is one of mankind’s most important modern challenges.
The Bio-economy
A bio-based economy - one which we use renewable biomass to produce the things our society needs - is often posed as a promising alternative to the burning of fossil fuels. But using sugar crops means competing with scarce arable land, while lignocellulosic biomass is still difficult to utilize efficiently. Cyanobacteria, which require mostly CO2 and light, hold great potential for sustainable production, but - compared to chemotrophs - are vexed by low productivity and often overlooked issues of genetic instability.
Genetic Instability
The problem is that cyanobacteria don’t like to allocate their carbon resources to biofuel molecules - they would rather use them to grow instead. Consequently, novel gene insertions quickly accumulate mutations that render them inactive, giving these mutants a growth advantage that filters out the producing strain. As a result, photobioreactor runs often face sudden declines in productivity, a massive problem when it comes to large-scale implementation of cyanobacterial bioproduction.
Our solution
Combining the best of cyanobacterial sustainability and chemotroph productivity
Synthetic Consortium
the idea is simple: we engineer cyanobacteria to produce simple carbon compounds using CO2 and sunlight in ways that are genetically stable. These molecules are shared with a chemotroph like E. coli, which uses them to produce a desired end-product, like commodity chemicals, pharmaceuticals, or biofuels.
The Goal
In our proof-of-principle consortium, E. coli produces isobutanol (an important biofuel) to highlight its sustainable production potential. But our engineered Synechocystis strains are essentially fully modular cyanobacterial production engines, and can be coupled to any biotechnological production process to remove dependencies on crops or petrochemicals and make it truly sustainable.
The project
Working together to save the world
The chemotroph
The workhorse of synthetic biology, E. coli benefits from the availability of a well-categorized genetic toolbox, making it the ideal chemotroph candidate for our consortium. We aim to engineer biofuel production in E. coli for use in our protoype consortium. Moreover, we intend to engineer interactions with Synechocystis in order to create a genetic safety switch that ensures our consortium only functions when its members are together.
The phototroph
Also known as the ‘Green E. coli’, Synechocystis is a model organism that growns on CO2 and light. We want to engineer Synechocystis to produce and share carbon compounds in ways that are genetically stable by coupling this production to its own growth. This essentially results in a modular phototrophic production egine. By then connecting Synechocystis to E. coli in our consortium, the latter would receive a continuous supply of sustainably-produced compounds required to produce virtually any desired end-product.
Such an endeavour requires several tasks. The two organisms have to be genetically modified to synthesize the desired molecules, preferably in an stable fashion. We also need to characterize how these new activities influence the physiological parameters of each bacteria, i.e. how fast they grow, what is the production rate, how stable are these rates, etc. These parameters can be used to build models that allow us to understand the dynamics of the system. Last but not least, the production in the resulting consortium has to be compared with other consortia.
Dry lab
Our modelling efforts will generate simulations of consortium development and will allow us to assess and use optimal organism ratios for the production of a desired end-product. Moreover, we intend to leverage genome-scale metabolic models to create a suite of open-source software tools that can be used to construct genetically stable and safe synthetic consortia in which a phototrophic species functions as the carbon provider for a product-producing chemotroph.
Consortia
Synechocystis and E. coli work well together, but are far from the only possible members of a synthetic consortium. Yeast, for instance, could be of great interest to the biotech community when coupled to our cyanobacterial production module. Alongside our main proof-of-principle consortium, we will therefore develop a micro-droplet screening protocol to rapidly assess the viability of novel consortia. This would greatly reduce trial-and-error time in the lab and allow users to identify consortia that serve their biotech requirements.