Ginkgo Bioworks Awarded Grant for AI-enabled Forecasting of Measles Outbreaks

Ginkgo epidemiological modeling experts and Northeastern University researchers awarded new grant from the Bill & Melinda Gates Foundation


Today we’re thrilled to announce that we’ve been awarded a grant from the Bill & Melinda Gates Foundation to build an open-access, AI-enabled measles forecasting model to empower proactive public health measures, such as immunization campaigns, in partnership with Northeastern University researchers Alessandro Vespignani and Sam Scarpino.

Measles is a highly contagious and often severe disease that most commonly affects children.

While the widespread availability of measles vaccines has dramatically reduced the disease burden over the past several decades, cases are on the rise in the U.S. this year, and global outbreaks continue to cause significant illness and mortality, particularly in low- and middle-income countries. These consequences are largely preventable through early interventions, but getting ahead of major outbreaks is difficult when access to data is limited.

With support from the Gates Foundation, expert epidemiologists and modelers from Ginkgo Bioworks and Northeastern University will develop a measles forecasting model to assess the risk of outbreaks and inform decision-making for timely interventions. Because measles reporting is often sparse, especially in low-resource settings, the model will draw upon traditional and non-traditional data, including public health reports, travel patterns, economic activity, and other factors, and utilize AI approaches such as machine learning and deep learning to structure and analyze a multitude of data sources to produce actionable insights.

“With support from the Gates Foundation, our project with Ginkgo Bioworks sets a new standard for what can be achieved when academia, industry, and philanthropy come together to develop global health solutions. By bringing together the expertise of multiple sectors and modern AI capabilities, we can create powerful, innovative tools that will provide critical information for safeguarding communities worldwide against the threat of measles.”

Alessandro Vespignani, Director of the Network Science Institute and Sternberg Family Distinguished Professor at Northeastern University

The forecasting model will be available open-access to help the global health community understand how likely it is that measles will emerge and spread within a given area, with the intent of enabling them to better allocate scarce resources and reduce the global burden of measles.

If we wait until large pockets of measles show up in hospital systems to launch public health responses, we are missing a critical window to act and slow the spread of this debilitating and highly contagious disease. Modern data and AI tools can shift the biosecurity and public health paradigm from reactive to proactive by helping global health leaders make more timely, effective decisions to prevent outbreaks from happening in the first place.

We believe the technologies we’re developing will give us the ability to get ahead of the curve for measles and other biological threats.

Next-Gen Enzyme Development for Sustainable API Manufacturing with Prozomix

We’re so excited to announce our new partnership with Prozomix, a UK-based biotech company focused on novel biocatalyst discovery and manufacturing!

Together, we aim to build out the production of next generation enzyme plates for active pharmaceutical ingredient (API) manufacturing. This collaboration aims to leverage Ginkgo’s Enzyme Services and industry-leading AI/ML models along with Prozomix’s existing enzyme libraries and deep experience manufacturing enzyme plates.

This agreement also marks Prozomix’s entry into the Ginkgo Technology Network!

Ginkgo’s Technology Network brings together a diverse array of partners, spanning AI, genetic medicines, biologics, and manufacturing, with the aim of integrating their capabilities to provide customers with robust end-to-end solutions for successful R&D outcomes. With Prozomix now in the Technology Network, Ginkgo customers will have access to Prozomix’s scalable contract manufacturing services, including enzyme samples from mg to kg scale.

For several decades, demands for both improved supply chain sustainability and reduction of costs of goods sold has driven the pharma industry towards the adoption of biocatalysts in commercial API manufacturing. Existing enzyme plates offer users an opportunity to rapidly screen potential candidates early in development to identify and de-risk the use of biocatalysts capable of supporting specific reactions in API manufacturing routes. As such, biocatalyst adoption largely depends on the diversity and performance of the enzymes available in these plates.

Prozomix and Ginkgo are partnering to usher in a new generation of biocatalysts built off of sequences and activity data from previous enzyme libraries.

Ginkgo will build class-specific AI models informed by enzyme sequences and data from its own massive metagenomic database as well as Prozomix’s enzyme libraries and associated screening data. These models can then be used to discover novel functional enzyme sequences. Prozomix intends to then use next-gen enzyme libraries, designed by these models, to manufacture novel enzyme plates.

Together, we expect these next-gen enzyme plates to have a diversity and performance that traditional plates lack, potentially unlocking biocatalytic opportunities where previous plates have failed. These plates will be freely available to all pharma process chemistry groups, provided that screening data is shared back with Ginkgo to drive further refinement of the Ginkgo AI/ML models.

“With a global reputation for de-risking early stage biocatalytic processes, we believe the Ginkgo partnership will keep Prozomix at the forefront of best in class biocatalyst provision throughout the AI revolution, enabling our customers to continue saving and improving more lives.”

Simon J. Charnock, CEO of Prozomix

API manufacturing is poised to greatly benefit from the latest in enzyme engineering and AI/ML enzyme models.

We are so excited to partner with Prozomix to get enzymes into as many API routes as possible and help partners meet both their COGs savings and sustainability goals.

To learn more about Ginkgo’s Enzyme Services, please visit https://www.ginkgobioworks.com/offerings/biopharma-enzyme-services/

Producing Novel Proteins to Control Ice in Extreme Cold Weather Environments with DARPA

Ginkgo has been awarded a contract for up to $6 million from the Defense Advanced Research Projects Agency (DARPA) to achieve DARPA’s objectives under its new Ice Control for cold Environments (ICE) program.

DARPA’s ICE program aims to develop new materials that control the physical properties of ice crystals to facilitate operations in extreme cold weather environments, which can pose a variety of risks to both personnel health and critical equipment. To meet this goal, Ginkgo, in collaboration with Netrias, Cambium, and consultant Dr. Ran Drori, aims to develop novel biologically-sourced and inspired materials that leverage biological adaptations to cold environments.

The Ginkgo team will work to enable the sustainable production of novel de-icing proteins with ice-modulating behaviors to improve operational efficacy in extreme cold weather environments.

These materials will be designed with the goal of meeting U.S. Department of Defense specifications and could potentially be used in solutions with broad commercial applications. One such application could be a lens coating to prevent frost formation for a range of optics applications from satellites and high altitude imaging instruments to security and wildlife cameras. The aviation and automobile industries could also benefit from de-icing products that facilitate safe operations in icy conditions. Furthermore, a topical frostbite prevention product could be developed for outdoor enthusiasts. If successful, these solutions could impact high value and consumer markets and facilitate replacement of current environmentally harmful de-icing agents.

The team plans to leverage Ginkgo Protein Services to design, screen, and optimize a library of novel proteins that demonstrate ice-modulating behaviors.

Ginkgo will design a library of proteins using metagenomic discovery and de novo computational design to source known, naturally occurring ice-modulating behavior proteins. During the discovery phase, predictive models will be used to iterate Design–Build–Test–Optimize loops, maximizing discovery of proteins with ice inhibition, induction, and low-adhesion properties. Throughout the process, Ginkgo will selectively screen promising proteins with further high-performance, application-specific characterization to inform the final down selection.

We are honored to be selected by DARPA to work on this program to facilitate sustained cold weather operations.

Building high-throughput libraries of candidate proteins is possible thanks to Ginkgo’s unique and differentiated data assets. Biology offers us a myriad of ways to adapt to our environment, and synthetic biology allows us to tap into nature’s capabilities and apply them to our own needs. We look forward to the products that the ICE program generates, which may enable enhanced safety and proficiency across various use cases.

To learn more about Ginkgo Protein Services, please visit https://www.ginkgobioworks.com/offerings/protein-services/.

If you are interested in working with Ginkgo for the public sector, check out our Offerings for Governments page.

Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the Defense Advanced Research Projects Agency.

Producing Animal-Free Non-Whey Dairy Proteins with Imagindairy

 

Today we’re thrilled to announce our new partnership with Imagindairy!

Together, we aim to deliver a global solution for animal-free non-whey dairy protein production in a highly cost-effective manner.

  • This collaboration will leverage Ginkgo Protein Expression Services and Imagindairy’s process development and scale-up expertise to accelerate the development of functional non-whey dairy proteins.
  • This is a multi-year program, funded in part by a joint grant from the Board of Governors of the Israel-U.S. Binational Industrial Research and Development (BIRD) Foundation.

Imagindairy envisions a cutting-edge transition in the dairy industry that preserves the flavor, functionality and experience of dairy without relying on cows. Imagindairy combines its proprietary AI platform with the age-old art of precision fermentation and uses microorganisms to create sustainable, scalable dairy proteins, without sacrificing quality, flavor, or nutritional value. With access to its own fully operational production lines, a first in the industry, Imagindairy is able to produce cost-effective dairy proteins at scale.

Imagindairy and Ginkgo have partnered to design an optimized organism capable of cost-effectively producing non-whey dairy proteins. This will allow Imagindairy to remain focused on whey protein production and commercialization while accelerating time to market of non-whey proteins. In tandem, Ginkgo will utilize its AI and high throughput Foundry capabilities to engineer biological systems for improved production economics and functionality. Imagindairy will then develop the production process and perform scale-up and manufacturing of these proteins, marking a significant milestone in their mission to provide a full range of high-quality, animal-free dairy proteins to food producers.

“Ginkgo has firmly established itself in the alternative dairy and food proteins industry, showcasing our leadership in protein and organism engineering. We have many successful collaborations in this space, and we’re thrilled to get to work with Imagindairy on this innovative and market relevant project. We’re also honored to be recognized by the BIRD Foundation. Being awarded this highly competitive grant is a testament to our technical expertise and ability to accomplish this project with Imagindairy. I can speak for the entire team when I say that the samples that Imagindairy have shared are absolutely next-level. If the rest of their pipeline is anything like what we’ve tasted, we can’t wait to try what’s next.”

Jennifer Wipf, Chief Commercial Officer at Ginkgo Bioworks

“We’re proud of this acknowledgment by the BIRD Foundation, as it highlights the importance of further innovation in the alternative proteins field, and our capability to successfully execute this project. Our process development capabilities and industrial-scale precision fermentation lines will allow us to rapidly scale the optimized strains created with Ginkgo and bring innovative non-whey proteins to the market faster. We’re deeply impressed by Ginkgo’s work in the foodtech industry and look forward to collaborating with them on the project. We’re confident this collaboration will unlock further product offerings, providing consumers with additional animal-free dairy delights that match the cost and taste of traditional dairy, making significant contributions to the industry, consumers, and the world.”

Eyal Afergan, Co-Founder & CEO at Imagindairy

To learn more about Ginkgo Protein Expression Services, please visit https://www.ginkgobioworks.com/offerings/protein-services/

Low Viscosity Aspergillus niger: Your Key to Enhanced Productivity

Enhance Your Commercial Enzyme and Protein Production

If you’re interested in fermentation-based production of enzymes and proteins, chances are you have heard of the filamentous fungus, Aspergillus niger. It is an efficient factory for making everything from citric acid to a variety of industrially relevant enzymes and proteins. But if you know A. niger, you’re likely aware of the challenges in engineering and fermentation scale-up that limit its potential applications for commercial production. Addressing these challenges requires hefty investment into developing suitable host strains. This is where Ginkgo can help. Our solution is a scalable, low viscosity best-in-class production host of A. niger designed to help you achieve your commercial production goals.


The Challenge

A. niger has long been valued for commercial-scale enzyme and protein production for a variety of factors:

  • High native production of industrially relevant enzymes and proteins
  • “Generally recognized as safe” (GRAS) by the FDA making an easier path towards commercialization
  • High-level protein secretion systems that reduce recombinant protein degradation by intracellular proteases and make downstream processing easier and cheaper

High Viscosity Fermentation
A major challenge of working with A. niger is its high viscosity fermentation, caused by long filamentous structures known as hyphae, which make production and purification difficult. Thick cell culture presents challenges in oxygenation, reactor mixing and nutrient feeding in scaling, which reduces enzyme and protein expression as well as making product recovery almost impossible. These factors may lead to increased time, cost, and resources required for commercial production.

Low-Throughput Strain Engineering
Beyond these challenges in manufacturing, strain improvement in A. niger is complicated by low transformation efficiency, difficulty in isolating correct edits from multinucleated cells, difficulty in automating HTP workflows because of filamentous growth, and secretion of many native proteases which can degrade the product. This can lead to longer, more expensive, and less predictable R&D programs to develop new products using A. niger as an expression host.

Our Solution: A Low Viscosity A. niger Expression Platform
We are pioneering new innovation in filamentous fungi-based manufacturing. We have applied our platform to create a new proprietary low viscosity A. niger production chassis, which we believe is a major advance against all of these challenges, and shows great promise for the development of other host strain expression platforms. By decreasing viscosity of our host strain, we unlock the ability to increase feed rate, oxygen transfer, and ultimately achieve higher expression rates for enzymes and proteins. The result? Increased titers at significantly reduced time and cost compared to conventional high viscosity strains.

 

Video (7 seconds): Fermentation process in a 10L reactor demonstrating Ginkgo’s low viscosity Aspergillus technology. The opaque broth contains a high cell density critical to industrial fermentation, yet low viscosity of the Ginkgo technology enables smooth continuous mixing with standard, scalable CapEx.

Solutions For You

Value of Low Viscosity Fermentation

  • Reduced Energy Consumption: Lower viscosity requires less energy for stirring at the same biomass levels therefore contributing to lower COGS.
  • Enhanced Biomass Yield: With a low viscosity phenotype maintained at a constant stirring rate, higher biomass levels can be achieved as we can unlock increased feed rate and oxygen transfer. This increased biomass can be attributed to increased production, improving protein titers and decreasing cycle time per batch, therefore lowering manufactured COGS.
  • Streamlined Downstream Processing: The lower viscosity phenotype facilitates potentially easier downstream processing and purification, simplifying the overall production workflow.

Generating a scalable low-viscosity A. niger manufacturing platform means an easier path to commercialization. We achieved this phenotype by integrating base strain screening with rigorous fermentation process optimization. Our novel base strain shows reduced filamentation in culture, and our optimized process – achieved through strategic changes to media composition, pH and feed rates – promotes enhanced growth of our strain without needing improved aeration strategies. We can promote high efficiency sporulation on agar plates for starting cultures and aiding recombinant gene transfer, and also prevent sporulation in liquid media that causes batch-to-batch variations in bioreactors and other processing issues. Through these methods, we have generated a base production strain optimized for low viscosity growth in scale-up fermentation.

The improved process created by our low viscosity strain and the strain’s genetic make-up which included multiple copies of the target enzyme, allowed us to improve production of a native secreted enzyme to 120 g/L, five times higher than our initial titers. With further strain engineering, there is potential to achieve even higher performance for this protein. These successes present opportunities for manufacturing other native products of A. niger to achieve similar titers. With the development of a fully validated fermentation process from 250 mL to large-scale industrial bioreactors we have helped reduce risk and associated R&D costs for future programs.

Chassis Strain Development
We can offer solutions for customers interested in developing their own chassis strain. We have identified several genomic mutations that confer the low-viscosity phenotype, and have confirmed that the equivalent edits replicate the phenotype in other fungal species. We see potential to engineer other filamentous fungi, including existing production strains, with similar phenotypes to generate multiple low viscosity expression platforms.

Development of a Clean Background
Using multiple gene editing approaches – a combination of classical split marker homologous recombination and CRISPR – we made significant improvements to our strain background. We performed targeted knockouts of multi-copy genes for secreted proteins that would compete with heterologous products, and for major protease genes and those related to protease regulation that can result in degrading your targets. Through these modifications of the host strain, we have generated a clean background strain with diverse project applications.

Strain Engineering Standardization
In parallel to developing a scalable fermentation process, we made fungal strain engineering more efficient and predictable. While filamentous fungi are notoriously difficult to engineer, we have developed efficient transformation protocols. We made the strain compatible with our platform by creating high-throughput transformation protocols that can leverage our in-house liquid handling robots and other clonal separation technologies, streamlining the process further. These improvements can give you confidence in our ability to express a variety of heterologous enzymes and proteins.

Conclusion

Expanding the scope of products that can be manufactured in filamentous fungi like A. niger offers immense industry value. Our breakthrough low viscosity expression platform stands as a key innovation, enhancing oxygenation and feed to maximize titer output of industrial enzymes and proteins. By combining our low viscosity strain with extensive R&D efforts, we’ve not only pushed titer limits but also simplified scale-up fermentation and optimized strain engineering processes. We’ve taken on the heavy lifting for you, streamlining production and reducing fixed manufacturing costs. With our proprietary high-productivity, low viscosity strain of A. niger, we’ve eliminated the complexities of strain development. This means you can feasibly achieve faster, more cost-effective commercial-scale production with reduced risk.

We’re equipped to engineer your strains and any enzyme or protein of interest in our production host. Stay engaged with us as we continue to push boundaries and uncover the full potential of A. niger.

Learn more about Viscosity in our Foundry Theory Video!

Hard Biology: Viscosity

In Summary

Our ready-to-use proprietary Aspergillus niger strain delivers:

  • Low viscosity – also in your own preferred production strain
  • High production of native enzymes and proteins
  • High-level enzyme secretion system
  • Clean background – Minimal native secreted protein / protease activity

Work With Us

Partner with us to unlock the potential of Aspergillus niger today!

Contact our technical consultants to learn more: Peter PuntKenneth Bruno

Engineering Biology: Advancing the Bioproduction at Ginkgo’s Cell Engineering Platform

Ginkgo Bioworks’ cell engineering platform lowers the bar for entry into developing products through metabolic engineering.

High-throughput strain design and testing on industry-leading chassis strains, paired with AI-enhanced enzyme engineering tools provides Ginkgo’s partners rapid prototyping and development. Nádia Parachin, Senior Director of Business Development at Ginkgo discusses how this streamlined process enables quicker market entry, fostering a lower barrier to bringing new products to market.

Humans of Ginkgo Bioworks is an interview series featuring Sudeep Agarwala interviewing some of the brilliant folks at Ginkgo to learn more about the technology that makes our work possible.


Sudeep Agarwala: You’ve run projects for quite some time at Ginkgo, but before that, were spanning both academia and industry, correct?

Nádia Parachin: Well I’ve been at Ginkgo for almost four years now, but you’re right–I came to Ginkgo from Brazil. In Brazil, I was a professor at Universidade de Brasilia and at the same time, I was the Co-Founder and CEO of Integra Bioprocessors. Integra used metabolic engineering to convert agro-residues (glycerol, for example) into high-value chemicals. And in fact, two of the technologies that we co-developed at Integra and UnB was a microbial strain producing PLA from glycerol and another strain producing Hyaluronic acid from sugar.

But that also naturally led to this position at Ginkgo. Since 2020, I have run quite a few projects at Ginkgo through the Foundry in yeast–Saccharomyces cerevisiae. What can I say? It’s my favorite yeast.

SA: Recently you’ve made an interesting shift–you’ve moved over to the commercial side, thinking about how Ginkgo’s platform can be applied widely to different companies?

NP: What is most impressive to see at Ginkgo during these years is not only once but–to my knowledge–at least a few times, the production of molecules that have never been made in a microbial host before. I’ve seen the same for enzymatic reactions. At Ginkgo, we demonstrated reactions not found in nature, truly contributing to the company’s mission of making biology easier to engineer. 

The reason for these success stories is the combination of our physical platform–automated, high-throughput strain design, construction, and testing– paired with our digital assets– incredible database of enzyme engineering experimental results and now AI-enabled engineering tools.  An equal player in this is the expertise of the people who run these workflows and design the experiments at Ginkgo. We have a collection of people who have deep knowledge of the different microbial hosts and have been working for years on critical pathways and developing tools to make this engineering possible.

What I find exciting about being on the commercial team is that my team’s technical expertise can be teamed up with people who have a real understanding of the market, resulting in tailor-made offers for what the market demands. It has been a fun journey, and I’m thrilled to be part of this team.

SA: Maybe to go into more detail here, what exactly does Ginkgo provide to its partners?

NP: Ginkgo provides our partners with a head start–partially because of the platform and our knowledge-base–technical assets we’ve collected over the years. So if a partner comes to us and wants to make an innovation in their field, they don’t have to invest in their own lab space, expensive specialized equipment, etc. They can get started very quickly by leveraging Ginkgo’s R&D capabilities and running experiments for a fraction of the cost of building a lab from scratch. This means they have a lower barrier to explore which  product has the potential to make a real difference in the market. 

We’re also providing value to the companies already in the field, who are already doing synthetic biology and fermentation. These companies know what they are doing in terms of their technology, their market. They have a good understanding of their processes for commercialization. But with our expertise, we can take on newer, earlier-stage projects instead of these companies having to rearrange their internal R&D: let us do your innovation, and when the technology is mature, you can incorporate it into your pipeline–you do the manufacturing and the commercialization.

SA: I’m curious about the difference between Ginkgo and CROs. When does it make sense to come to Ginkgo vs. say, going to a CRO?

NP: We see this question come up all the time. The most important difference is that besides our platform and a proprietary database, Ginkgo has developed and owns what we call “chassis” strains: microbial hosts that have been modified for increasing flux throughout key metabolic pathways.

Take the shikimate pathway, for example. This pathway can produce multiple molecules, ranging from building blocks for polymer production to flavors, fragrances, and nutraceuticals.

When you go to a CRO to engineer a product off the shikimate pathway, you have to start from scratch to develop dedicated enzymes for your target’s pathway. In parallel, you also have to develop a strain that will have a high flux through the shikimate pathway to get your product to your target titers.

But when you’re working with Ginkgo, our starting point is lightyears ahead. We’ve already developed the base assets, our ‘chassis’ strains that have flux through the shikimate pathway at very high levels. So now we dedicate our work to the specific part of our customer’s pathway that converts this flux into their target molecule. And because it’s only this part, we can deliver both prototyping and strain development faster than any other CRO. 

I’m talking about the shikimate pathway here, but it also applies towards fatty acid metabolism, terpenes, any range of pathways that you’re engineering off of. You’re not starting from scratch–you have the starting strain, the platform, the enzyme engineering capabilities, and that gives you a head start towards commercialization. 

SA: So this is a compelling reason for leveraging Ginkgo’s platform, but I’m curious what happens if too many people start to do that. Like you’ve acknowledged, there’s a big market in metabolic engineering for small molecules. How does Ginkgo think about protecting information between different companies who are coming to Ginkgo?

NP: This has come up a few times as a major concern from people who are talking to us. We’ve had partners who have said “Look, I know you guys have a project with my competition. Can you guarantee that there’s not going to be any sharing of my information?”

And one of my arguments for the companies in industrial biology has been that we aren’t just doing small molecules: we have pharmaceutical companies on the platform–that’s the standard that we’re working with to ensure that there’s no sharing of information between different projects for different companies. We have that capability and we take it very seriously. We’ve developed systems internally that flag information so that it cannot be shared and that data that results from one customer’s project cannot be shared.

The entire point is that Ginkgo prepared itself over the years to be positioned at the cutting-edge of synthetic biology technology, and we’re working towards utilizing the platform to enable the sustainable production of biomolecules applied to several industrial sectors. It’s not just about engineering strains, it’s also about creating a bioeconomy and seeing it thrive. And we’ve made it possible so people can develop their strains and bring their products to market with confidence that they’ll be competitive.


Nádia Skorupa Parachin, Ph.D., is Senior Director of business Development at Ginkgo Bioworks, leading the Industrial Biotechnology sales team for the production of small molecules. Nádia brings over 15 years of experience in synthetic biology, metabolic engineering, and project management. She has previously served on the technical team at Ginkgo as a Senior Program Lead, engineering and delivering custom strains for Ginkgo’s partners. Before joining Ginkgo Bioworks, she was CEO of Integra Bioprocessors and a professor of biotechnology at Universidade de Brasilia (UnB).

Biological Chassis: Yarrowia Lipolytica & Fatty Acids

Yarrowia lipolytica has become a workhorse for metabolic engineering of molecules derived from fatty acids.

In cars, a chassis is a base frame to house the engine and working parts. Program Director Christian Lorenz discusses how Ginkgo developed standardized strains, workflows and DNA parts for the yeast Yarrowia lipolytica to help launch innovative biological engineering campaigns.

Humans of Ginkgo Bioworks is an interview series featuring Sudeep Agarwala interviewing some of the brilliant folks at Ginkgo to learn more about the technology that makes our work possible.


Sudeep Agarwala: I’m speaking from my personal bias, but when I think of yeast I usually think of Saccharomyces cerevisiae. Why is Yarrowia lipolytica such a powerful tool?

Christian Lorenz: Sure–I think there’s a good reason you don’t think of Yarrowia when someone mentions yeast. Most people would probably agree that Yarrowia is still a non-traditional yeast, but given how important it is in industrial biotech, there’s a lot more interest in the yeast for academic circles.

Basically, as the name suggests, Yarrowia lipolytica has been of interest because of its ability to accumulate lipids, or fat. We’ve seen natural strains accumulate 20 percent or more dry cell weight in lipids–I believe there are some reports of 40%, even. Some engineered strains can even have a higher content of fats.  So Yarrowia is an expert in making fat and has a high flux through the fatty acid biosynthesis pathway.

This pathway is upregulated when the cells experience nitrogen limitation–there’s a starvation response that triggers lipid production. They utilize the carbon in the media, usually in the form of glucose, but in the industrial setting it can be something cheaper like ethanol, glycerol, acetate, or even different types of oil, and start accumulating fat, which are stored in lipid bodies in the cell.

SA: But there are a lot of yeasts that produce fatty acids–what’s so special about Yarrowia that it’s able to do it at such high levels?

CL: This is something that’s in common with an entire family of oleaginous yeasts, they’re called. In these yeasts, the precursors for the fatty acid synthesis pathway–acetyl CoA, which converts to malonyl CoA. In oleaginous yeasts, citrate is produced in the mitochondria; it is shuttled into the cytosol, where an enzyme, ATP citrate lyase, converts it into acetyl CoA, which leads to fatty acid biosynthesis. The flux through this pathway is much higher in these yeasts.

SA: This lifecycle seems pretty great for metabolic engineering — I know Yarrowia’s a workhorse for metabolic engineering off the fatty acid production. And in protein production, it’s great for lipase production.

CL: Lipases, and a lot of other hydrolytic enzymes too. But there’s an interesting use in small molecule production as well: because of the metabolism, Yarrowia is a good acid producer and that usually means that it can tolerate low pH in fermentation. That’s important because for some yeasts, they die at low pH. So when you engineer these yeasts for some small molecules that drop the pH, you have to add a lot of base to your fermentation. That’s not the case for Yarrowia, which we’ve seen do well as low as pH 3, even.

SA: That’s the good — I want to talk about the ugly, though. Yarrowia is known as a dimorphic yeast, meaning it has ovoid cells, but can also form these filaments that can cause real issues when it comes to fermentation. How do you deal with that?

CL: This is a really good point. First of all, we have a collection of more than 30 different naturally-occurring strains of Yarrowia at Ginkgo that we’re allowed to engineer with. Each of these strains are Yarrowia lipolytica, but they differ a lot in how they behave in how we engineer them, and how they behave in different fermentation processes. So for any particular engineering project, we have a wide choice of strains that we can test to see which ones will behave the best in our process.

SA: I feel like we’ve buried the lede — Ginkgo has more than 30 different wild Yarrowia strains?

CL: Sorry — yes. More than thirty, and we’ve gotten them being very careful about restrictions on freedom to operate and IP restrictions. And we’ve done a lot of work characterizing them: there’s the obvious questions about how they behave on solid medium on a petri dish vs how they grow in a liquid medium. But we’ve tested them further: how much flux do they have through the fatty acid biosynthesis pathway? In different fermentation conditions how tolerant are they to different process conditions? how well do they tolerate different pH? etc. We’ve gained quite a bit of information for them, so we can make intelligent decisions about how we deploy them in different engineering projects.

SA: What does it take to be able to genetically engineer more than 30 different Yarrowia strains?

CL: Well, we think about strain engineering in a Design-Build-Test-Learn cycle.

In terms of Design, we have standardized DNA tools that we know will work in most, if not all, of these strains. That is, we have standard promoters, terminators, drug selections on these engineering tools. And they’re targeted to parts of the genome that we know are easy to target.

That leads to Build, where we’ve developed methods of culturing and effectively introducing this DNA into these strains pretty effectively–transforming a wide range of these hosts in high-throughput is a pretty standard operation at Ginkgo.

For Test, like I mentioned before, we have a good understanding of how these strains behave in a wide variety of conditions–liquid media, solid media, and fermentation vessels. We know how to cultivate these strains in high-throughput so we can measure how much product–small molecule, protein, etc.–they’re producing.

SA: I hope you don’t mind the direct question, but at Ginkgo we refer to “chassis strains” when we’re developing an engineering plan. What exactly is the Yarrowia chassis at Ginkgo?

CL: I think we’ve done a good job summarizing that here, actually. A chassis is a frame or a housing for a piece of technology. Part of our engineering efforts at Ginkgo have been to make that framework in Yarrowia: we have strains, genetic tools for targeting and expressing DNA, protocols for building libraries of yeast strains in high-throughput, and protocols for testing these different strains in high-throughput. There will be some edge cases, always, but with these basic elements form a very powerful framework for biological engineering.

So when a new project comes in, we don’t have to think about developing things from scratch or bringing in new yeasts and spend a lot of time testing them or developing processes for them. Instead, we have our engineering chassis: we’ve built the engineering infrastructure for Yarrowia so that our customers can bring exciting products to the market fast.


Christian Lorenz came to Ginkgo Bioworks after completing his PhD work on bacterial protein secretion systems with Ulla Bonas at Martin-Luther-Universität Halle-Wittenberg, and post-doctoral work on Pseudomonas aeruginosa in the lab of Stephen Lory at Harvard Medical School in Boston. At Ginkgo, he is an organism engineer specializing in metabolic engineering for small molecule production in bacteria and yeast systems.

Engineering Biology: Partnering with Protein Services

Ginkgo’s Protein Services leverage a diverse technological platform to provide support our partners’ R&D.

Sneha Srikrishnan, Senior Director of Business Development at Ginkgo, discusses how Ginkgo’s business model customizes partnerships to align with the developmental stage of partners’ products, offering tailored R&D services from strain engineering to fermentation optimization. 

Humans of Ginkgo Bioworks is an interview series featuring Sudeep Agarwala interviewing some of the brilliant folks at Ginkgo to learn more about the technology that makes our work possible.


Sudeep Agarwala: Sneha, you’ve been at Ginkgo more than seven years and have done everything from strain development workflows in the foundry all the way to talking to customers about how Ginkgo approaches protein expression issues. 

Sneha Srikrishnan: Well actually, I’ve been thinking about protein production for my entire professional career–I researched this as a graduate student and postdoc and you’re right–when I first came to Ginkgo, I was working on developing a lot of the early workflows in the foundry for engineering different types of yeast. It’s been incredibly gratifying seeing those workflows grow into what Ginkgo’s offering now and it’s also why I’m so eager to talk about Ginkgo’s place in protein production in my current role in business development at Ginkgo.

SA: I know you’ve talked here about how Ginkgo works with partners in the protein space. I’d like to get a sense of how the partnering work–an earlier-stage product may have a very different scope of work associated with it than a more mature product that is already out on the market. So how does a company’s stage in R&D play a role in how we partner with them?

SS: We’ve thought about how to work with a wide range of partners in the protein space and the different stages of products that they’re working on. You’re right that early-stage products may require more extensive R&D in terms of strain engineering or other aspects of product development. Add to this, many early-stage products, either at start-ups or at larger, more established companies, may not have a lot of cash to outsource R&D–either because people are working on these early-stage products as a preliminary proof-of-concept to see if it has legs or because people are still working on funding for their company.

Late stage products can have a different scope associated with them. And by this, I mean, projects that are already on the market, so maybe there’s less strain development and more emphasis on fermentation optimization, processing, with less of an emphasis on strain engineering.

In my previous conversation, I’ve talked about how Ginkgo’s Protein Services’ Offerings are aimed to help projects at a wide variety of stages. But there’s another important point to discuss here in terms of how we try to maintain flexibility in our business model with these service offerings, and structure it so that we are tying our success to the success of our partner.

In general, we divide the cost of a project into two buckets. There’s an R&D fee, which we don’t generate margin from. The second bucket is downstream value–and this is where we tie our success to the success of our partners.

Realizing downstream value can be in the form of royalties on sales, a flat percentage of revenues, lump-sum payments on commercial milestones, or any combination of these. Or, for whatever reason, if it doesn’t make sense to have this payment tied to sales, we’ve been able to find ways to solve these situations as well–single payments, or a single payment broken up into different chunks; we try to be flexible on how this downstream value is realized and we try to work with our partners on how this can work.

What I’m trying to emphasize here, though, is that Ginkgo wants our partners to be successful, and that we’re willing to work with our partners to index on that success.

SA: I think maybe you’ve answered this question indirectly, but I want to make sure: when does it make sense to come work with Ginkgo versus, say, a CRO?

SS: I like this question because I get it in different ways from many potential partners. I think of it like this: companies can go to CROs with a very defined service that they are looking for–in many instances, this is the kind of work that companies have the capability but not the bandwidth to do or can’t justify the expense to do in-house for a project that might be in its very early stages. 

Ginkgo’s cell engineering platform is different. The goal of developing this platform is to bring a wide range of technologies to bear on a single project; and in some cases we’ve combined part of the platform into our Service Offerings, which makes sure that we’re providing state-of-the art technology on our partners’ R&D.

SA: And, I suppose, there’s an effect of streamlining the work through Ginkgo in these Service Offerings, versus having to coordinate with a lot of different CROs or academic groups.

SS: Exactly–there are efficiencies when you’re bringing a product to market with Ginkgo, and this is what makes it a great place for companies interested in end-to-end research and development. In progressing your project from early stages–discovery or early strain development–all the way to fermentation optimization and scale-up, there’s an efficient knowledge-transfer that comes between the different teams working on your strain that can really shave a lot of time off your commercialization process. Imagine if instead you have to tech transfer from and to a different CRO every time you needed to move to the next stage of your project.

And there’s one other point that I think is worth mentioning here–that efficiency brings with it flexibility. Let’s say for example you’re developing a strain using rational engineering methods and are hitting a wall with reaching the target titers. Ginkgo can quickly move to unbiased engineering methods without having to identify a partner who can do this work.  We know how to do this quickly because they are already part of our broad platform: the teams for rational engineering and unbiased engineering collaborate to provide new direction to the project (sometimes they’re even the same people). And this is how we can quickly shift gears to this new direction in the project.

We think about this efficiency in our platform in terms of “more shots on goal” at making a project successful. I think this is something to really emphasize: you can potentially mitigate a lot of technical risk by working with Ginkgo. Having many workstreams easily accessible in one place allows you to try different things quickly as you move forward to commercialization. And at a place like Ginkgo, we’re there to support the development that needs to happen so you can focus on the product-facing work needed to commercialize your protein.


Sneha Srikrishnan is Senior Director, Business Development at Ginkgo Bioworks, leading Protein sales & Product management. She previously served on the technical team of Ginkgo as a Sr. Director of platform technology for enzymes and protein production. Prior to Ginkgo, Sneha worked at Gevo, Inc. as a scientist developing yeasts for commercial production of isobutanol. She has over a decade of industrial experience in successfully delivering synthetic biology-based solutions within the nutrition & wellness space, in sustainable fuels, waste valorization and environmental remediation, and holds patents in these areas. Sneha graduated with a Bachelors in Chemical Engineering from the Indian Institute of Technology, Bombay and earned her Ph.D. in Chemical and Biochemical engineering from the University of California, Irvine. Sneha is passionate about food security and circularity.

Ginkgo Biosecurity Launches Doha-Based Pathogen Monitoring Center, CUBE-D, Establishing Middle East Hub for Global Bioradar, at Qatar Free Zones

Today we’re pleased to announce the signing of an agreement with Qatar Free Zones Authority (QFZ) and Doha Venture Capital (DVC) to build the first Center for Unified Biosecurity Excellence in Doha (CUBE-D) within Qatar Free Zones.

  • CUBE-D’s advanced platform is expected to serve as a nucleus for global pathogen monitoring efforts and be a key hub in Ginkgo’s bioradar network.

  • The partners believe that CUBE-D will establish Qatar and its free zones as pioneers of biosecurity innovation, enabling the growth of the country’s bioeconomy by bringing highly skilled jobs and businesses to Doha, as well as bolstering biosecurity infrastructure in the region and the world by strengthening Ginkgo’s global bioradar capabilities.

  • With the new site in Doha providing expanded monitoring capabilities into the Middle EastAfrica, and Asia, and connecting into Ginkgo’s existing network across the world, the launch of CUBE-D will bring the world closer to the goal of creating global infrastructure to protect against biological risks.


The signing took place alongside QFZ’s and DVC’s participation in the Web Summit Qatar, in a ceremony attended by HE. Dr. Ahmad Al-Sayed, Minister of State and Chairman of QFZ/DVC, HE. Mohammed bin Ali Al Mannai, Minister of Communications and Information Technology (MCIT) and Vice Chairman of QFZ/DVC, and Matthew McKnight, General Manager for Biosecurity, Ginkgo Bioworks, along with executives from the ministry and the three signing entities.

Supporting global programs modeled in part after the U.S. Centers for Disease Control and Prevention (CDC) Traveler Genomic Surveillance (TGS) program, which tracks and analyzes pathogens collected at seven international airports in the U.S., CUBE-D will be a foundational piece of biosecurity and health security infrastructure in Ginkgo’s multi-continent, integrated early warning system for biological threats.

CUBE-D plans to support analysis of data collected from pathogen monitoring stations in both Qatar and partner countries, such as airports, municipalities, and agricultural sites by leveraging cutting-edge analytical platforms powered by artificial intelligence and developed by Ginkgo. Environmental and other anonymous, non-clinical samples will be regularly scanned for signals of emerging outbreaks, offering insight into how pathogens travel and evolve and building detection capabilities for natural, accidental, or intentional biothreats.

Advanced sequencing and bioinformatics tools aim to pinpoint the genetic signatures of pathogens and provide early warning for global health and national security leaders in as close to real-time as possible. Coupled with Ginkgo’s leading epidemiology and risk analytics platforms, this type of biointelligence will feed into predictive models to facilitate rapid response, such as medical countermeasures, before a biological threat impacts lives and economies.

H.E. Dr. Ahmad Al-Sayed, Minister of State and Chairman of QFZ and DVC: “We are delighted to welcome Ginkgo Bioworks, a pioneer in the biotech space and an anchor player joining an expanding community of innovative companies, within the free zones in Qatar. Ginkgo’s partnership with our tech development fund, DVC, will foster innovation and enhance the overall biotech ecosystem within Qatar and the broader region. At QFZ, we are aiming to become a place of choice for companies shaping the future of the biotech industry. We look forward to supporting and collaborating with Ginkgo Bioworks in their establishment and growth in the region and beyond.”

Jason Kelly, CEO of Ginkgo Bioworks: “The world needs effective biosecurity. Building hubs like CUBE-D to connect Ginkgo’s network of international biosurveillance nodes transcends regionalism and lays a foundation for the future. After all, biology doesn’t respect borders. I am proud of Ginkgo’s ability to technically and socially synthesize this global immune system, one node and hub at a time. Everybody’s health is connected, and CUBE-D is a foundational step forward for global biosecurity.”

Matthew McKnight, General Manager of Biosecurity at Ginkgo Bioworks: “CUBE-D represents the next generation of biosecurity infrastructure. By leveraging lessons from COVID-19, Ginkgo is building a global bioradar system to detect a wide range of known and unknown biothreats.  As a central connectivity hub with over two-thirds of the world’s population within an eight-hour flight, we believe Qatar and its free zones are ideally positioned to anchor these bioradar efforts.”

Rwanda’s Minister of State for Health, Yvan Butera: “As inaugural members of Ginkgo’s global pathogen monitoring network, we are extremely supportive of expanded regional investment in high-end monitoring solutions and excited to have the opportunity to continue growing our biosecurity capabilities by leveraging partnership with the new Ginkgo CUBE facility in Doha.”

Strain Engineering and Process Development to Deliver Enzyme Expression Systems

Our partner encountered a bottleneck in accessing and producing a key enzyme required for scaling-up their vaccines.

By leveraging Ginkgo’s cell engineering platform, our partner was able to develop an E. coli expression system for their enzyme expression. Combined with fermentation and processing protocol, we achieved a ten-fold increase in efficiency within a year.


Strain Engineering for Bio-Based Industries

Enzymes play a crucial role where traditional chemical methods are inadequate. Perfected through millions of years of evolution, these biological catalysts guide cellular processes with unparalleled precision. The capacity to extract these proteins from their natural environment and employ them to catalyze specific reactions has sparked a revolution across various industries, spanning from basic chemicals to pharmaceutical drug manufacturing. Industry stakeholders have recognized that substituting traditional exotic chemical catalysts with enzyme-based solutions often provides more adaptable, powerful, and cost-efficient alternatives for product development, while also potentially diminishing their ecological footprint. To preserve their competitive advantage, companies persistently seek innovative approaches to enhance enzyme production processes.

Ginkgo Bioworks’ Cell Engineering platform streamlines biological engineering via state-of-the-art, well-developed workflows. While traditional strain engineering can be a protracted and high-risk endeavor, our approach involves organizing our extensive experience and knowledge base into these workflows, resulting in a more efficient path for developing industrially-relevant strains and processes. This structured approach not only reduces the time spent searching for solutions but also empowers our partners with best in-class strain engineering for accelerating their product development, and ultimately, scaling to commercial manufacture.

The Challenge: Overcoming Enzyme Supply Constraints for Vaccine Production

Our partner, advancing vaccine production to meet global demands, faced supply chain limitations with a critical enzyme needed for their manufacturing process. Despite exploring commercial sources, they encountered a shortage. In-house production attempts fell short of scale-up requirements, highlighting a pressing need for a commercially viable production method for this essential enzyme.

Our Work: From Sequence to Manufacturing in less than One Year

We approached our partner’s protein expression problem by initiating two concurrent workflows: first, a Strain Engineering workflow was deployed, aimed at identifying elements that optimized the expression of their enzyme in E. coli

Design: We developed a very targeted library of roughly 300 DNA expression constructs that we predicted would have a high probability of improving enzyme expression. The library tested different DNA recodings of the protein (while maintaining amino acid sequence), promoters, plasmid backbones, ribozyme variants, and ribosome binding sites (RBSs).

Build: Within weeks of designing these constructs, our in-house DNA synthesis team delivered these plasmids, which were transformed into the E. coli expression host.

Test: By the time these strains were constructed, we had developed a targeted set of enzyme titer and activity assays. We screened the ~300 member library for enzyme expression of each of these library members, selecting the top-producing strains according to our assay. 

Simultaneously, we launched the Fermentation Process Development workflow alongside strain engineering. Initially, we pinpointed critical fermentation parameters, and used statistical techniques (Design of Experiment–DoE) to optimize the process based on identified parameters. By the time we established an effective protocol, strain engineering had identified promising candidates suited for this optimized fermentation.

Our Process Development team selected the best-performing strain and began industrializing the fermentation process to guarantee scalability. This phase focused on adapting our development to meet large-scale production needs, addressing potential scale-up challenges in advance.

This involved tailoring the fermentation media to support regulatory requirements for vaccine manufacturing. In doing so, this workstream also monitored the robustness of the fermentation feed profile making sure that the strain we were using was genetically stable throughout the entire fermentation run.

This dual workflow strategy ensured continuous knowledge exchange between the two streams of development, allowing us to effectively inform and enhance each phase. This synergy enabled us to deliver a scalable solution to our partner within their timeline.


The Outcome: Empowering a vaccine-manufacturing breakthrough

  • Rapid Results: In under a year, our partner saw a 10-fold increase in protein yield from their starting point due to an optimized strain and fermentation process.
  • Strain Engineering Success: Within the first six months, a single Design-Build-Test cycle reduced 300 potential strains to 22, achieving a 5-fold yield improvement.
  • Fermentation Optimization: From the 22 strains, a single top performer was selected through Fermentation Process Development, performing well in scaled fermentation.
  • Overall Improvement: The combined optimization efforts led to a 10-fold improvement over the initial strain, with industrialization ensuring scalability.
  • Knowledge Transfer: The final two months focused on transferring our findings, enabling our partner to significantly surpass their previous year’s enzyme production in a single run.
  • Market Entry: Leveraging exclusive rights to the newly developed process, our partner scaled up production to enter the global vaccine market.


Our Capabilities:

  • Rational Strain Engineering: Ginkgo’s library of DNA parts and experience with a wide variety of host organisms means shorter development time and higher probability of success. Paired with analytics, Ginkgo’s Cell Engineering Platform, efficiently executes Design-Build-Test workflows to identify top-performing strains.
  • Streamlined R&D: Pairing strain development with process development identifies strains that not only function well in the laboratory but translates that activity into the fermentation tank and industrial setting.
  • Industrial Optimization: Development workflows take into account the constraints of manufacturing products at scale from developing industry-relevant protocols to monitoring genetic stability at scale.
  • Tech Transfer: Successful projects require smooth integration into our partners’ pipelines. Our engineers are experienced in developing knowledge transfers and troubleshooting, empowering our partners with the technology we develop.

Work With Us

Ginkgo Bioworks’ Cell Engineering Platform brings actionable bio-based solutions.

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