Ginkgo Bioworks Fires Up Its Bio Foundry To Take On The Billion-Dollar Enzyme Market

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Ginkgo Bioworks is getting ready for another year of disrupting the entire biotech industry model with its versatile menu of biology engineering services. As a full-stack synthetic biology service provider, Ginkgo does everything: from developing new flavors and fragrances to engineering entire organisms for crop treatments and living medicines. Over the last year, Ginkgo has been making moves into biopharma, and now they have announced a new Enzyme Intelligence service. I recently chatted with Jason Kelly, one of Ginkgo’s co-founders and current CEO, who will be speaking at SynBioBeta 2023, to get more details on the company’s latest offering.

The move into enzymes is not surprising: with applications from biopharma to agriculture, enzymes are a multi-billion-dollar market. These molecules are tiny biological machines that can carry out versatile functions – from keeping our bodies running to catalyzing massive-scale reactions in the chemical industry. In the human body alone, there are over 2,700 enzymes and many of those are targets for treating disease. For the chemical industry, enzymes are important tools that make and break chemical bonds. And for the bioeconomy, they are essential drivers for building a sustainable future.

Regardless of the area of application – be it food, pharma, skincare, textiles, chemicals, or anything else that can be built with biology – enzymes are biology’s workhorses that convert sustainable inputs into valuable products. But each specific product or application involves developing and perfecting custom enzymes for optimal performance. This process, called “enzyme engineering”, requires extensive R&D: from developing computational algorithms that suggest which enzyme may work best for the task at hand to figuring out which host organism to use for its production. The timelines for developing each new enzyme are excruciatingly long, and results do not always justify the upfront investment.

Ginkgo Bioworks is saying – drop all that: “That’s the big shift we’re trying to create in the market. We want people to stop doing their own in-house R&D and leverage our platforms,” thinks Kelly. “We can take you all the way to a commercial enzyme from a concept.” This may be an attractive proposition for many companies that may not want to invest in their own R&D efforts and simply need the job done. Ginkgo promises not only to take that work off their hands but do it better and faster.

Making more enzymes, faster

Enzyme engineering and commercial production has been around for a while. But what has changed in the last decade is the industry’s demand for these molecules. In the past, academic labs and companies could spend years tweaking a single enzyme, but now biomanufacturing is putting pressure on enzyme engineers to deliver these biocatalysts today so that we can meet the sustainability goals of tomorrow.

Developing great enzymes required both expertise and infrastructure. Depending on the task at hand, some enzymes may need to be optimized for enhanced performance or improved stability in harsh reaction conditions; other projects may call for developing a new enzyme to carry out a unique reaction for which there is no equivalent in nature; and sometimes all you need is to scale up the production of an already existing enzyme. Regardless of the goal, Ginkgo can take care of everything from design to manufacturing process optimization.

For example, during the pandemic, Ginkgo collaborated with Aldevron to improve the production of its vaccinia capping enzyme, a critical component used in the manufacturing of the COVID-19 mRNA vaccines. The company quickly recognized this potential bottleneck for vaccine manufacturing and worked on improving the enzyme production host strain and optimizing the fermentation conditions. Thanks to Ginkgo’s improvements, Aldevron could make 10 times more enzyme per batch than with the previous process.

Building the world’s largest database of enzyme sequences

Scaling up is, no doubt, important for tapping into the full enzyme market potential. But the real challenge in the industry is designing and engineering novel enzyme functions that do not exist in nature. The design is powered by Ginkgo’s sophisticated software built on machine learning algorithms. Other companies like Cradle, Biomatter Designs, Cambrium, Arzeda, and Basecamp Research are also using the power of machine learning and AI to design novel enzymes or improve existing ones. They analyze gene sequences from public and proprietary databases and use predictive models to “write” new enzyme sequences.

If you know anything about models, you know the axiom that the model is only as good as the dataset it has been trained on. This is where Ginkgo Bioworks has a massive advantage. Ginkgo’s Codebase, which the company refers to as their “biological portfolio”, contains DNA sequences that can be used to train the machine learning algorithms to recognize the features that contain the desired qualities for enzyme engineering: “Because we run our labs like factories,” says Kelly. “We’re generating systematized data at a rate that no one else is and that’s why our models are so good.”

Ginkgo has invested heavily in both the digital and physical infrastructure. Over the last few years, Ginkgo has gone through impressive growth and now has close to 1,200 staff after the recent acquisition of Zymergen. The Zymergen acquisition was like a nesting doll for building capacity: not too long before the merger, Zymergen had acquired Radiant Genomics which had developed an industrial platform for natural product and gene discovery. Zymergen had also purchased another company called Lodo Therapeutics that had compiled a vast collection of environmental microbial DNA.

These acquisitions have been a part of a deliberate effort to curate the best genome database out there. In 2019 Ginkgo invested in buying Warp Drive Bio for their genome mining platform, with microbial collections gathered from pharma companies: “There has probably been five or six of these proprietary big microbial sequencing efforts done and we’ve acquired three of them. So, when we say we have a big proprietary genomics database, we mean it,” laughs Kelly.

Ginkgo says its database currently contains close to 1 billion sequences, and all that wealth of genetic information is available to their customers: “It’s just a service contract away from anybody that wants to develop a product,” says Kelly.

From conception to production under one roof

Biology is incredibly complex, so every model-generated sequence still needs to be tested in the lab. The Codebase is just “the fuel for the design engine”. The actual physical powerhouses where the computer-generated enzyme concepts are built and tested are Ginkgo’s Foundries. The Foundries are high-throughput labs that contain the latest automation, software, and analytics – which includes its own DNA synthesis platform and state-of-the-art fermenters – to be able to manufacture and screen thousands of strains and discover the best enzymes.

As a startup – or even a multibillion-dollar international giant like Merck – you have a choice: to build all that infrastructure yourself or outsource. Kelly thinks it is a no-brainer: “You can come and outsource a big project to us and that will take a big load off of you.”

“What we really want to drive home to our customers is that you don’t need to do it yourself – we have invested half a billion dollars into infrastructure and automation so you don’t have to,” says Kelly. ‘We succeed when our customers succeed’ is the philosophy Ginkgo is banking on.

Thank you to Katia Tarasava for additional research and reporting on this article. I’m the founder of SynBioBeta and some of the companies I write about, such as Ginkgo Bioworks, are sponsors of the SynBioBeta conference and weekly digest.

Forbes Business
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