Scaling Up: Synthetic Biology’s Bottleneck
Carbon-negative manufacturing is locked by a current inability for synthetic biology companies to make use of economies of scale.
Synthetic biology has the potential to revolutionize the bioeconomy, allowing for the highly efficient production of natural products through carefully controlled biochemistry. The bottleneck1 on the biomanufacturing revolution is scaling up production from small, several liter benchtop cultures to thousand or ten-thousand liter tanks.
Hundreds of synthetic biology startups and scientists are working on bioproducing materials, enabled by tools like CRISPR and cheap DNA read & write. But the promise of synthetic biology depends on economies of scale, and scaling up production is a gargantuan task.
For one, there is just limited tank space. 90% of synthetic biology technologies fail to get out of the lab because of scaling issues. Reportedly, companies wait 18 months to get partnered with fermentation facility. Timescales like that are sure to sink startups. There are not physically enough big steel tanks available.
Building on the financing end of this problem is Synonym, which invests in fermentation infrastructure and has a fermentation facility database called Capacitor. Capacitor in total over 30 million liters in fermentation capacity, but current facilities are mostly bench or pilot scale. Synonym suggests many customers are looking for facilities at a scale which doesn’t even exist yet. All reports point to how we need much more space (on the order of billions of liters, not millions). Analogizing to the software industry, imagine if there just wasn’t enough cloud compute available for everyone who needed it.
Deciding how to scale up production is riddled with challenges too. The debate between scaling up (switching to larger-volume bioreactors) versus scaling out (adding capacity by using additional, smaller fermenters) is not straightforward. Scaling up suffers from high energy costs, higher risk in the case of infection, and problems with foaming and heating up. Scaling out has higher up-front costs for installation, material, and maintenance.
There is a ton of room for innovation in this scale-up step of biomanufacturing. So far, I’ve seen a few companies working on alternatives to traditional microbial fermentation in steel tanks: Future Fields wants to replace microbes with fruit flies, and Chi Botanic wants to manufacture products in plant cells. There are businesses working on financing (Synonym), cell-free systems2 (Solugen, Sutro Biopharma, Debut Biotech), and optimization (Ori Biotech, Vineti), but in general, the infrastructure side of the industry comes across as wildly underdeveloped.
Some reasons cited for these concerns include an oppressive regulatory environment with slow adoption times, and little in the way of industry standards and guidance. The government is paying more attention to the industry though, so there’s some chance of this changing.
I would personally love to see people work on dealing with infection control (as a way for companies to avoid losing large volumes of product), artificial intelligence-powered optimization to tune fermentation parameters (like temperature, fermentation time, and so on; there are some odd 15 levers to pull here), and designing more flexible fermentation facilities to take on a variety of clients.
Biomanufacturing is a challenging hard-tech space with an upside that will go on to define the sustainable manufacturing practices of the future. In recent years, software startups have benefited tremendously from access to cheap data centers and cloud computing platforms that scale with their needs. Developing and investing in infrastructure for synthetic biologists will similarly provide the ramp we need to accelerate into the bioeconomy.
This is the sort of thing that gets me really excited. If you’re working in the bioeconomy infrastructure space and willing to chat please do reach out to me!
Downstream processing also poses an enormous challenge.
Very very promising; Solugen is an amazing example of a company making money doing carbon-negative manufacturing.