Gingko Bioworks: Engineering The Future of Organisms

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Imagine if we could find a way to make practically every product in the world, from plastic to medicine to food, faster, cheaper, and more sustainable. It sounds unreal, right?

That’s synthetic biology, the design and construction of new biological parts, devices, and systems, and the re-design of existing, natural biological systems for useful purposes. Whether that be the design of plastics, medicine, or food.

Gingko Bioworks is one of the most astronomical synthetic biology companies of the past era.

While the founders of the company met nearly two decades ago, upon getting their Ph.D.’s, Gingko Bioworks started in Boston in 2009 as the team of 5 MIT scientists got together, intent on building microbes that could be produced to order, considering the organism as the product itself. Gingko calls itself “The Organism Company,” for the exactly right reasons; it is working to engineer and automate the next generation of organism design.

Gingko believes that within biological engineering, “living organisms are the factories that build new products.” In essence, they are designing the best organisms through automating and scaling the process of organism engineering, thus allowing thousands of biological designs to be prototyped.

Gingko Bioworks set out to create a company that integrates biology, software, and hardware and is now applying this process to many areas of synthetic biology, and now is working on projects in the realms of strain improvement, enzyme discovery, new product development, biosecurity, and mammalian cell engineering.

Gingko Biology provides the backend for the synthetic biology industry; designing and engineering microbes for a giant range of customer needs, from cannabinoid-producing bacteria to yeast that ferments next-generation of food proteins.

Gingko Bioworks is working on many projects from optimizing processes including optimizing the process for vaccines with Moderna, working on biosecurity with IARPA, the Intelligence Advanced Research Projects Activity, and discovering and testing antibodies with Berkeley Lights, a digital cell biology company working to accelerate the development and commercialization of biotherapeutics and other cell-based products. In the past, Gingko has engaged in many other endeavors and has spun out and funded many other projects, from designing probiotics for plants through Joyn Bio and enabling bioremediation solutions through Allonia.

Gingko Bio functions through a two-part system; foundries and a codebase.

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The foundries are Gingko’s biological factories. To design the living organisms that build new products, the essence of what Gingko does, they need factories to be able to design these organisms, with the best of DNA synthesis, laboratory automation, analytics, and software. Within its foundries, Gingko has capabilities such as strain engineering, DNA synthesis, and fermentation. The Bioworks foundries automate and scale the organism engineering process, allowing engineers to prototype thousands of biological designs.

On the other hand, Gingko’s Codebase acts as its biological portfolio. In the same way that software engineers use existing libraries of code to write new programs, Gingko’s organism engineers use Gingko’s growing codebase of cells, enzymes, and genetic programs to start new projects and drive new discoveries. Within its codebase, Gingko works to build living medicines, produce cultured ingredients, and work on biosecurity initiatives.

While Gingko’s foundries design, build, and test organisms and prototypes at a giant scale, the codebase grows as discoveries are made, projects are initiated, and connections are drawn.

Through the integration of its foundries and codebase, Gingko is building the backend of the bioeconomy.

In the past several years, Gingko has activated countless initiatives, projects, and discoveries within its hub. One of these projects, Joyn Bio, is a joint venture between Ginkgo Bioworks and Leaps by Bayer, and is engineering plant microbes to solve growers’ greatest challenges.

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Joyn Bio leverages Bayer’s expertise in plant biology and Ginkgo’s automated foundry to revolutionize agriculture. Through the power of the plant microbiome, Joyn improves strains of microbes, from pest control to enhanced nutrient acquisition and resistance to crop disease.

Due to high throughput automation, Joyn’s team of microbiologists and engineers can test thousands of samples at a time. This allows for a high-level analysis of thousands of microbe strains isolated from soil, and for the rapid prototyping of engineered strains, which are then tested in greenhouse and field conditions at Joyn’s testing facility in California.

Currently, Joyn is focused on significantly reducing agriculture’s reliance on synthetic nitrogen fertilizer used to grow crops such as corn, wheat, and rice, as the production and application of this fertilizer contributed to about 3% of global greenhouse gas emissions. Joyn is working on creating microbes that can produce nitrogen in the roots of crops who cannot do so themselves, and are currently in field trials throughout the United States.

Another initiative that Gingko Bioworks has worked on is the production of living medicines in partnerships with Synlogic, a company designing living microbial therapeutics.

Gingko realized that essential amino acids including leucine, isoleucine, and valine cannot be synthesized by the body. Therefore, the human pathways that are responsible for catabolizing these amino acids have many highly regulated enzymes, and mutations within them result in severe metabolic disorders. In order to combat this issue, Synolgic had been genetically engineering microbes to deliver the necessary functions missing in such diseases and had been prototyping an enzyme pathway to consume leucine within E. coli.

The pathway was initially designed with three different enzymes from yeast and bacteria. In order to optimize the pathway to increase the consumption of leucine, Gingko sources, synthesized, and screened over 1,200 homologs of each enzyme, finding the best performing enzymes that had significantly more in vitro activity than the original enzymes used for the pathway.

The top hits of each individual enzyme screening were then assembled into a library of 350 operons, or clusters of genes, and screened with a high throughput leucine consumption assay.

After more screening and optimization by Synlogic, the final optimized strain SYN5941 was 7 times more effective in leucine consumption than the original strain and was also shown to lower leucine consumption in other primates. This research was condensed into a paper published by researchers at both Gingko Bioworks and Joyn Bio.

This project served as an example of a successful transition of in vitro improvement into in vivo biological activity of engineered microbes. In 2019, Synlogic and Ginkgo expanded their partnership with a range of new projects, expanding Synlogic’s pipeline and helping to accelerate the discovery of more microbial candidates.

Gingko’s focus on building an ecosystem has played a key role in driving the discoveries of synthetic biology in the past era. The future of Ginkgo Bioworks is centered around building an ecosystem of companies that use Ginkgo’s biofoundry and codebase to accelerate their findings.

By setting up a wide variety of partnerships and working with companies on the edge of emerging tech within synthetic biology, as well as building a backbone model for discovery, Gingko Bioworks has been wildly successful.

The future of Gingko Bioworks holds the potential to transform industries, products, and science through its endeavors within synthetic biology.

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