1Synthetic biology: the multidisciplinary field has a vast potential and it’s evolving so fast that there seems to be no agreed definition for it. Let’s say that synthetic biology or SynBio is a way of engineering existing biological systems for useful applications. Biotech applications span across several industries, including in the production of food, fibre, drugs and biofertilisers. Industrialists and economists also expect SynBio to play a big role in sustainable economic growth.
But nature itself can be a barrier for SynBio to be sustainable. The living world generates biomass (biological materials) to grow in two separate ways:
- autotrophic organisms convert inorganic carbon (carbon dioxide) into biomass;
- heterotrophic organisms use organic molecules (sugars and fats) for growth.
Autotrophs (organisms that encompass plants) comprise of the most biomass on Earth, as well as supplying a majority of our food and fuels.
One problem with sustainable biotech is that most SynBio organisms are heterotrophs that grow on sugar. And producing sugar requires energy, and therefore, it’s challenging to build a sustainable economy driven by these organisms.
Sure, there are other autotrophic chassis for SynBio like moss, cyanobacteria or algae. All of these organisms generate sugars — which act as building blocks for biomass generation — from carbon dioxide and water through the autotrophic process, photosynthesis. My own SynBio research was on the moss Physcomitrella patens (see here for a lay summary). Moss and co. bring many benefits to the SynBio industry, but like all model organisms, they also have limitations. Bacteria and yeast seem to be the preferred industrial choice for many SynBio applications.
Why? Mainly because the process to genetically engineer these microorganisms are simple. And advancing molecular biology tools are making it easier to genetic engineer almost any model organisms. In other words, bacteria and yeast are seen as more profitable biotech organisms. Of course, bioproduction from environmentally sustainable model organisms also brings down the costs, but time is money — and in general, these microorganisms grow faster than other SynBio organisms.
Therefore, applying the principles of autotrophic growth to heterotrophic, SynBio organisms is vital for the growth of environmentally and economically sustainable biotech industries.
That’s why two separate groups of scientists recently converted bacteria (Escherichia coli or E.coli) and yeast (Pichia pastoris)* to grow using carbon dioxide — the most significant greenhouse gas — instead of sugar. How? By using the SynBio approach, of course.
*The link above for the yeast research is a preprint version of the final peer-reviewed article, which, at the time of writing this post, was behind a paywall due to the publisher’s embargo.
Research teams engineered the genomes of a bacterium and yeast, respectively to introduce the “Calvin cycle”: the natural autotrophic process that plants use to convert carbon dioxide into sugars. Scientists introduced the key autotrophic enzymes — including Rubisco, the most abundant enzyme in the world, which fixes around 90 percent of the world’s inorganic carbon — to enable microbes to fix carbon dioxide into biomass.
Simultaneously, researchers also deleted the enzymes that use sugars to generate biomass. As a result, researchers essentially rewired the central metabolic pathways of these organisms to convert them from heterotrophs to autotrophs.
Yeast and bacteria are central to the biotech industry. Therefore, these two studies are significant breakthroughs that set an important milestone towards sustainable SynBio production. These leaps in biotech open up the possibility to convert the carbon dioxide in the atmosphere into products that we use in our daily lives: food, medicine and fuels, to name a few.
The future bio-economy driven by these SynBio organisms may one day have a negative carbon emission. But, it’s still a distant dream, yet.
Let’s start by looking closer at the engineered autotrophic organisms. Both the synthetic bacteria and the synthetic yeast convert carbon dioxide to biomass (Calvin cycle) — and that’s great. But these organisms (and others) also have another central metabolism process to generate energy: the “Krebs cycle”.
The Krebs cycle breaks down organic molecules to release energy-rich chemicals that power the biochemical processes in cells. Therefore in autotrophs, there are two distinct metabolic processes: Krebs cycle, to generate energy; Calvin cycle for biomass.
The downside to the energy-generation pathway or the Krebs cycle is that — when it breaks down the organic molecules — it also releases a significant amount of carbon dioxide as a waste byproduct. For example, in the engineered E. coli bacteria, the energy-generation process releases more carbon dioxide than the greenhouse gas input in biomass-generation.
Previous studies show we can use carbon dioxide to make the same organic molecules (methanol and formate) that respectively enter the energy-generation process of yeast and bacteria. Scientists believe that in the future, we can feed the autotrophic organisms with the organic molecules generated from carbon dioxide. Combining these two approaches may help us implement circular bio-economy enabled by sustainable manufacturing at an industrial scale.
From producing medicines to meat alternatives and cleaning up environmental pollutants, SynBio has the potential to use industrial waste to manufacture useful products. As such circular economy built on SynBio industry could initiate a new sustainable industrial revolution helping cities achieve net-zero emissions.
Read the original research papers:
- Conversion of Escherichia coli to Generate All Biomass Carbon from CO2 — https://doi.org/10.1016/j.cell.2019.11.009
- The industrial yeast Pichia pastoris is converted from a heterotroph into an autotroph capable of growth on CO2 — https://doi.org/10.1038/s41587-019-0363-0. Or see the BioRxiv preprint version for open access — A synthetic Calvin cycle enables autotrophic growth in yeast https://doi.org/10.1101/862599
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