Many scientists can probably relate to putting a project away for years but still having it with them in a myriad of thoughts. At least that is the case for the CSO and co-founder of TriptoBIO, Johan Andersen-Ranberg. When he left the University of Copenhagen to pursue a postdoc at the University of California Berkeley, he left his Ph.D. project focusing on the biosynthesis of high-value plant natural products to collect dust on a shelf.
However, ten years later, after returning from abroad, Johan and a colleague started investigating parts of the project. After getting some breakthrough results in establishing a yeast platform to produce a complex plant molecule named triptolide early on, it suddenly became attractive to explore the project’s commercial potential. Still, he did not expect the project to lead to an early-stage company working on supporting safe rat sex to combat the damaging effects that rats cause.
How did you end up focusing on rodent pest management?
We knew from pharmacological studies that the compound triptolide from the Chinese plant Tripterygium wilfordii has immune-suppressive, antitumor, antifertility, and anti-inflammatory properties. These have been exploited for centuries in Chinese natural medicine. What we found out was that triptolide also works as a contraceptive agent in male rats, and that it is the critical ingredient in contraceptive rodent pest management solutions, a market that is growing exponentially in the US. However, the problem is that triptolide can only be obtained by harvesting the Chinese plant and you only obtain tiny amounts from this harvest, which makes the compound extremely costly. Thus, we started to investigate whether it would be possible to establish a sustainable supply of triptolide using a synthetic biology yeast platform.
This will facilitate the widespread adoption of contraceptive rodent pest management as an alternative to rodenticides, which are highly toxic and have an enormous negative impact on the environment and human health. I would be surprised if rodenticides are not banned within the next five years, making the market even more attractive.
Why was it challenging to develop a triptolide production platform with synthetic biology?
Triptolide is a diterpenoid with a unique shape, typically built around a carbon structure and decorated with oxygens sitting at specific sites. We needed to identify plant enzymes that catalyze a methyl shift to establish the biosynthetic production process. Such enzymes have never been found in plants before, and identifying and characterizing them allowed us to introduce them into yeast for the first time. Now, triptolide can be made in the same way as beer or wine.
Typically, many synthetic biology companies struggle with scalability regarding downstream and upstream processing. How do you cope with scalability?
The nice thing about this plant compound is that it has such high potency and high value. Many synthetic biology production platforms are required to provide many tons of a product to reach economies of scale needed to compete with existing chemical synthesis methods. We can serve the world market with an order of magnitude less, and because the price of triptolide is so high, we will still be profitable.
Chemical synthesis is nowhere near being cost-competitive with plant-based production. By being the first to offer an alternative source of triptolide, the chemical companies will have to beat us and not the other way around. For a complex molecule like triptolide, this is simply not possible with the state of the art in organic synthesis.
What is your focus during the Venture Lab program?
Our primary focus is to reach the gram scale since that is a requirement for obtaining a registration with the US Environmental Protection Agency. Then, our triptolide will be eligible for use in contraceptive rodent pest management solutions. We do not need to go through a lengthy regulatory approval process as the end product is already approved, on the market, and demonstrated to be safe.
Further, we are using the Venture Lab program to develop our business. We are excited about replacing poisonous rodenticides with a scalable and sustainable production of triptolide, but it is only the beginning. TriptoBIO is establishing a general synthetic biology platform for producing high-value plant compounds with low accessibility today. We are using the Venture Lab program to set the path for this journey.
What will be essential in becoming a successful company?
Speed to market! The market is growing, and we want to enter as quickly as possible to establish a global leadership position. This will also demonstrate the value of our production platform and allow us to expand to more high-value plant compounds that can benefit society.