In May 2020, a McKinsey report found that the global bioeconomy is slated to become a $4 trillion gold rush as synthetic biology’s promise to make high-quality, sustainable products gains traction. These products range from food to textiles to medicines, and biofermentation is the manufacturing process that makes all of it instead of having to extract them as natural resources. Today, we sit down with Nik Mushnikov, CEO and co-founder of AsimicA, whose technology promises to solve the bane of biomanufacturing: low yields that formerly could not compete with traditional manufacturing methods. Using his invention, dubbed “microbial stem cells,” Nik thinks he can achieve multi-fold yield increases in product, and keep the bioreactors running longer.
Ok first off, what is a biofactory, and why is everybody talking about them?
Microbial biofactories are basically reactions in which we use microbes (like a bacteria or yeasts) to make the product we want. This was a solution when the product itself was biological, like insulin, and we didn’t know how to engineer a synthetic process that is smarter than a living cell.
Now with genetic engineering, biofermentation is becoming more popular as we are learning how to make other products that aren’t even biological in nature. For example, we used to make plastics with petrochemicals because it was cheaper and more efficient, but the synthetic biology field is learning they can engineer microbes to make specialized plastics.
Wow, so do you think that biofermentation will be used to make everything?
I think petrochemical or chemical synthesis is still more efficient, but it comes with problems like relying on oil as a feedstock and toxic pollutants as a byproduct.
Microbes, on the other hand, have the potential to produce any chemical compound in a sustainable manner, using renewable resources, if you can engineer it correctly. If you factor in the externalities, I think that traditional chemical synthesis is starting to lose its edge, especially when it comes to specialized products.
Why isn’t everyone using biofermentation right now?
Microbial biofactories can’t operate non-stop. As they divide, every generation becomes less productive and you have to restart the entire batch. Every restart is expensive in terms of expensive, specialized labor and downtime. We’re talking several days. Economically this doesn’t fare well, and we need to find ways of making them more efficient and more productive.
People have tried ways to make the microbes live longer or more resistant, but evolutionary genetics eventually catches up and drives the population to become sickly and unproductive. The solutions in the past have been… lackluster.
So I guess that’s where you come in! How are you solving this problem of low yields?
Instead of trying to make the microbes live longer, we found a way to repopulate and replenish biofactories with a fresh generation of microbes during the batch. We’re doing it using our innovation of “Microbial Stem Cells.”
In our bodies, our stem cells essentially replenish the cells in our tissues so that they stay functional for decades, much longer than individual functional cells can live.
Our idea is similar to that — microbial stem cells are constantly replenishing the fraction of productive microbes in the bioreactor. It is a way to bring up new young and strong “workers” to the factory, so to speak. We’ve published mathematical models that show that this replenishment strategy would result in a 2–4 fold higher number of productive microbes in the bioreactor, which translates to higher productivity per reactor, and longer batch runs.
The effect that microbial stem cells can provide on bioreactor productivity can significantly increase the profitability of bio-manufacturing.
How did you come upon this insight? Was this always something you engineered with biofermentation in mind?
I was always very intrigued by the potential of biofactories for manufacturing all sorts of chemicals: pharmaceuticals, fuels, advanced materials, and so on. And I wanted to be involved in designing new strategies for bio-manufacturing using microbes.
When I started my PhD, I had a couple of projects, focused on increasing yields of microbial fermentation. The idea of realizing stem-cell-like behavior in industrial strains of microbes came out from previous fundamental research insights made by my advisor, Dr. Grant Bowman. He was studying a phenomenon of asymmetric cell division in some unique bacterial species. Sometimes their cell division diagram resembles the division of stem cells. Certainly, these species are not applicable to the industry. And molecular mechanisms underlying their asymmetry are way too complex to just copy them.
What we’ve done is that we identified a minimal set of key components that can induce asymmetric division in other species. We borrowed them from several different bacteria and transferred them into E. coli, and our Nature Chemical Biology paper demonstrated that we can indeed induce asymmetric cell division and program differentiation in different cell types.
What kind of products are you able to make and is there any limit to what yields you can increase?
We just got results last week that we are able to make several products from pharma, food, and the cosmetics industries. These are just proof of principle experiments to demonstrate how versatile our platform is. We’re thinking of experimenting with fuels next which are highly toxic products for microbes to make — again, just to flex how broadly applicable our “microbial stem cell” technology is.
Everyone who does biofermentation is dealing with the exhaustion of microbes, and I don’t think there is a better solution than ours to improve yields and lengthen batch reactor runs.
So the sky is the limit in terms of products, but what about the cells? Are you limited to E. Coli?
That is a very good point. Of course, not all biofactories are using E. coli cells as their workhorse. We see a fairly straightforward way to transfer out technology to other species of bacteria. We’re already working with Bacillus subtilis, which is what most of our industrial partners are using. Transferring our ideas to eukaryotic microbes, yeast, and fungi, would be a more R&D extensive project but we’re confident we can get there.
How does a potential partner incorporate their technology into their existing manufacturing process?
Biotech companies won’t need to change much in their manufacturing processes. What we do is a strain engineering service, which changes how the culture of cells in the bioreactor behaves, enabling microbial stem cell properties. But it doesn’t change the production process itself. Simply speaking, our partners would do the same things they were used to, but their strains after AsimicA modified them would have higher productivity.
Why did you study microbiology?
I started to learn about the broad potential of microbes back in high school and my interest kept growing throughout college. Each microbiology course taught me that the potential of microorganisms is unlimited. My first research project was in yeast genetics. I’ve learned some methods and practices of working with microbes, but the research scope was rather fundamental and driven by the needs of clinical biology, whereas I was more interested in applied microbiology.
I finally found The Bowman Lab in Wyoming to do my PhD, where my interests were more aligned with applied bio. There, I could perform my research studies, keeping in mind that we’re creating new tools, new technologies that can be directly applied to the industry. That research dynamic is closer to my heart, and launching AsimicA where I can take the application to industry has been one of the most rewarding experiences I’ve ever had.
What good would this do for the world?
The world needs cleaner economics. Humanity is facing existential challenges, and although we are getting closer to solving those challenges we still have a long way to go and perhaps what will move the needle the most is to change the way we make things — using renewable resources, reducing pollutants, and dropping down our emissions. Our technology can facilitate biofermentation in becoming the primary method for the production of the vast majority of chemicals. Just imagine how much dirty production we can push out if we can increase yields by 2–4 fold across the entire industry. That’s what I think AsimicA could do for the world and that’s the future that I want to help build for us.