In this report, we share results from the first few months of our collaboration with Lygos. Read on to learn how Lygos leveraged our bioproduction services to achieve more than 2-fold titer improvement compared to their starting strain and fermentation conditions.
Opportunity | Optimizing bioproduction to meet sustainability targets
Lygos was founded in 2010 to provide renewable solutions through biotechnology. Today, Lygos is a leading provider of high-performing and sustainable specialty chemicals that help customers meet their highest performance and sustainability goals. The company’s proprietary and fully integrated platform uses advanced biology, chemistry, and application development to convert low-cost sugar to high-value and multi-functional products. These ingredients are designed to create more sustainable supply chains and to transition the world towards better, cleaner, and more sustainable products.
One of Lygos’ renewable solutions is Ecoteria™ malonates, a line of products that Lygos manufactures from malonic acid derived through fermentation. Specifically, Lygos invented a way to harness yeasts to produce malonic acid by creating a malonyl CoA hydrolase (MCH) to more efficiently convert malonyl-CoA into malonic acid. This production method replaces an acutely toxic and vulnerable supply chain that is key to the production of fragrances, agricultural chemicals, pharmaceuticals, and other specialty applications.
Lygos saw an opportunity to further expand the market for Ecoteria™ malonate products through additional strain and enzyme engineering efforts.
Solution | Leveraging strain and enzyme engineering at Ginkgo
By partnering with Ginkgo, Lygos gained access to high throughput robotics infrastructure, AI/ML, genomic data assets and strain and enzyme engineering tools. Ginkgo’s cell engineering platform is capable of designing, synthesizing, and screening thousands of enzyme variants developed with machine learning or identified through an extensive proprietary metagenomic database. Furthermore, Ginkgo’s services give partners access to high throughput, automated workflows for transforming, cultivating and screening a variety of host species spanning bacteria, yeast, fungi and mammalian cell lines.
“We were thrilled to learn how Ginkgo’s codebase and automation could help us quickly test out ideas we had to improve strain performance, magnifying the capabilities of our own internal R&D efforts.”Eric Steen, CEO of Lygos
For this program, Ginkgo planned two parallel approaches that leverage both strain and enzyme engineering. The first approach tests a small set of MCH enzyme variants in a variety of yeast production hosts; the second tests a variety of enzyme variants in a select few yeast production hosts. After an initial round of screening, the top-performing combinations of enzyme variants and yeast hosts are tested head-to-head in industrially-relevant fermentation conditions. Ginkgo deploys its ambr250 systems for this, which have demonstrated reproducible results at industrial scale.
Outcome | A step change in production economics in just 4 months
Just four months into the collaboration and using the first approach described above, Ginkgo developed a new yeast strain and fermentation process that demonstrates a >2-fold improvement in titer compared to Lygos’ control strain.
This strain incorporates Lygos’s engineered MCH in a host that Ginkgo had previously characterized and validated. Optimization of the fermentation process with the new strain further improved titer in industrially-relevant fermentation conditions. In addition to the >2-fold improvement in titer, this new strain demonstrated significant increases in production rate, and yield as compared to Lygos’s previous best-in-class.
Even greater improvements are expected on the horizon through the ongoing enzyme and strain engineering work. These advancements and the achievement of the first program milestone has placed the partnership on an exciting path forward.
“Collaborate to Accelerate is a key strategy at Lygos that focuses on working with best-in-class partners to increase efficiency and speed, accelerating our time to market. We are pleased with the initial results of our collaboration with Ginkgo and look forward to continuing this partnership.”Eric Steen, CEO of Lygos