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/

GreenLab Selects Ginkgo Enzyme Services to Develop Novel Enzyme That Breaks Down ‘Forever Chemicals’

We’re thrilled to announce our new partnership with GreenLab, an emerging next generation plant-biotechnology company!

GreenLab is developing a product with the purpose of degrading PFAS and will leverage Ginkgo Enzyme Services to discover a novel enzyme of critical importance for use in this application.

Ginkgo Enzyme Services provides companies with end-to-end enzyme discovery and optimization R&D services. Given its extensive expertise in this space and the nature of this particular project, Ginkgo is providing these services under its success-based pricing model, created to help companies de-risk their research and development efforts.

Cornfield Factories

GreenLab’s proprietary technology allows it to grow enzymes and other proteins inside a corn kernel. By producing proteins in a cultivated crop, GreenLab can readily scale up production across acres of cornfields, with little additional up-front capital and infrastructure.

After the protein of interest is extracted from the kernel with minimal waste, most of the corn used will then proceed along the existing value chain, including food, feed or fuel. GreenLab already has two transformative proteins in commercial production, including manganese peroxidase (a multipurpose environmental remediation solution) and brazzein (which delivers a high-intensity sweetness).

The PFAS Problem

PFAS, short for “per- and polyfluoroalkyl substances”, describes a group of manufactured chemicals that have commonly been used in nonstick and waterproofing agents for decades. They bear the moniker of ‘forever chemicals’ owing to their enduring nature and inability to break down in the environment. They are associated with many dangerous health effects including cancer, reproductive and immune system harm, and other diseases.

A Kernel of Hope: Bio-Based Solutions to Break Down PFAS

There is currently no known commercial process for degrading these forever chemicals, but GreenLab is on a mission to change that and reverse their perpetual environmental buildup. PFAS degradation is a significantly complex problem, and currently no PFAS-degrading enzymes have been commercialized. GreenLab aims to tackle this difficult enzymological problem by leveraging Ginkgo Enzyme Services to discover and develop a novel enzyme for use in their PFAS degradation application. This project is the first step in a journey that could potentially lead to the first deployment of a commercially viable enzymatic solution that can degrade one of the most recalcitrant chemicals in existence.

Ginkgo Enzyme Services

Ginkgo will lead an metagenomic discovery campaign leveraging its vast metagenomic database to identify a library of PFAS-degrading enzymes. Ginkgo will then use advanced ultra-high throughput screening methods to identify unique enzymes with desired activity and transfer the best candidates to GreenLab. In later stages of this collaboration, Ginkgo will further engage in AI-enabled enzyme engineering to further improve on the discovered enzyme.

“GreenLab is eager to work with Ginkgo towards solving such a massive and prevalent environmental and health problem. By leveraging Ginkgo Enzyme Services to conduct our enzyme discovery and development, we believe we’re enabling our R&D team to produce, pilot, and deploy our product faster and with less risk than any other option we considered.”

Karen Wilson, CEO of GreenLab

At Ginkgo, we say that our partners can find the needle they’re looking for in our tech stack.

We are thrilled to be working with GreenLab on PFAS degradation, and are ready to utilize our platform to solve such a challenge. We’ll be deploying our powerful AI-enabled in-house computational tools, best-in-class enzyme Codebase, and ultra-high throughput screening methods as we seek to find a novel enzyme fit for GreenLab to address this globally important enzymological problem.

Allonnia, the bio-ingenuity company™ dedicated to extracting value where others see waste, plans to work with Ginkgo and GreenLab to help discover a novel enzyme to combat PFAS, and will work with GreenLab as a commercial partner deploying the enzyme in their end-to-end PFAS solution. In doing so, Allonnia is furthering its commitment to the identification of a biological solution for PFAS degradation. The company has already introduced a PFAS separation and concentration solution with EPOC Enviro’s SAFF unit, a sustainable PFAS remediation technology. Integrating a process for the biodegradation of PFAS concentrate discovered through this project into Allonnia’s solution would represent a breakthrough closed-loop approach. Additionally, Allonnia believes that this solution could be expanded in the future to serve as a degradation technology for other applications where there is a significant unmet need today, such as in-situ soil remediation.

To learn more about Ginkgo Enzyme Services and how you can access Ginkgo’s success-based pricing, visit ginkgobioworks.com/enzyme-services/.

What will you grow with Ginkgo?

Synlogic Leverages Ginkgo’s Cell Engineering Platform to Develop Potential New Treatment for Homocystinuria

Interested in leveraging Ginkgo Enzyme Services for your R&D? Get in touch here

Executive Summary:

Synlogic designs and develops Synthetic Biotics — living biotherapeutics based on engineered bacteria — with the potential to provide safe, convenient, orally-administered, non-systemically absorbed new medicines for serious diseases. The company has a focus on rare metabolic diseases, including homocystinuria (HCU), which is characterized by elevated levels of total homocysteine (tHcy). Patients are at risk of both acute, life-threatening events and severe complications. HCU treatments aim to reduce tHcy levels in patients, firstly through limiting intake of methionine, an amino acid precursor to homocysteine found in many foods. Synlogic recognized the potential of methionine as a target for a Synthetic Biotic and partnered with Ginkgo to improve the activity of their initial prototype biotherapeutic candidate.

Synlogic and Ginkgo set out to increase the activity of methionine degradation, focusing on the key enzyme Methionine Decarboxylase (MetDC). Leveraging Ginkgo’s Enzyme Intelligence suite of tools, Ginkgo delivered genetic parts that multiplied methionine degradation activity in vitro, including a new MetDC enzyme with more than four-fold higher activity. Within a year of initiating the program, Synlogic incorporated these components into their prototype strain and evaluated the activity of the optimized strain, SYNB1353, in mice and nonhuman primates.

Opportunity | Developing living medicines for a genetic disease

Based in Cambridge, Massachusetts, and founded in 2014 by MIT professors Jim Collins and Tim Lu, with support from Atlas Ventures, Synlogic designs living medicines for diseases with significant unmet needs. The company uses synthetic biology to genetically engineer probiotic bacteria (Escherichia coli Nissle 1917) and generate living medicines designed to metabolize or synthesize validated biological targets of known disease pathophysiology.

One disease Synlogic is targeting is homocystinuria (HCU), an inherited disorder characterized by risks of elevated homocysteine. The build-up of homocysteine can lead to multiple adverse effects, including bone defects, intellectual disabilities, and life-threatening blood vessel obstructions. Treating HCU aims to lower levels of total homocysteine (tHcy); a cornerstone of treatment is restricting dietary methionine, an amino acid found in protein-containing foods, and which is a precursor of homocysteine.

Joanna, who lives with HCU and has endured two strokes, seizures, and vision impairment because of this disease said, “We need to come together as a community and do more. Nobody knows how devastating HCU can be… We must continue to focus on research and work to develop new treatments. In the meantime, I want those living with HCU to know they are not alone and there are people who want to help.”

Current treatment options for HCU are limited in terms of safety, tolerability, and efficacy, underscoring the need for a new, innovative approach: Synlogic engineered a Synthetic Biotic to target and metabolize methionine as a means of lowering tHcy levels to treat HCU.

Solution | Boosting microbial metabolism for human disease

In developing a Synthetic Biotic for HCU, Synlogic sought to improve two activities of their bacterial strain: the methionine importer that transports methionine into the bacterial cell, and the methionine decarboxylase (MetDC) that efficiently converts methionine into non-toxic compounds to prevent tHcy accumulation.

Ginkgo’s protein engineering team took two approaches to improving these components. A metagenomic approach searched through Ginkgo’s extensive multi-billion protein database for a biologically diverse set of candidate enzymes. In parallel, a protein engineering approach applied predictions from machine learning models in combination with structural analysis to design variants of the two proteins with a high likelihood of improved functionality. Combined, these approaches identified roughly 2,000 candidate methionine decarboxylases, and a targeted library of roughly 150 candidate methionine importers.

DNA for the enzyme libraries was synthesized and transformed into Synlogic’s strain background. In parallel, Ginkgo’s engineers developed a bespoke, high-throughput assay that would test the functionality of the importer protein and MetDC proteins. Once the DNA was synthesized and transformed into the screening background and the bespoke assay was on-boarded onto Ginkgo’s high-throughput automation platform the strains were screened in high-throughput in Ginkgo’s Foundry. The team identified an importer and decarboxylase that, in combination, showed significant improvement over Synlogic’s previous prototype. Synlogic was able to verify that these two new proteins improved their strain’s methionine degradation in vitro.

Outcome | Developing new treatments for human disease

Within a year, Ginkgo’s collaboration with Synlogic resulted in the naming of the investigational new drug, SYNB1353. The drug successfully demonstrated proof-of-mechanism in humans by showing the ability to degrade methionine and reduce its plasma levels using a dietary model. This is the first investigational new drug developed on Ginkgo’s platform. It was granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track designation by the FDA. Next steps for the program include a Phase 2 study in patients with HCU. SYNB1353 offers a potentially new, orally administered, and non-systemic approach to degrade methionine, thereby lowering tHcy and its associated risks and daily disease burden of HCU.

“As a company, we are in regular contact with leaders and members of the HCU community, who continually express their appreciation for our efforts to bring something new forward,” said Mylene Perreault, PhD, Head of Research at Synlogic. “It is very powerful to hear directly from patients and caregivers about how transformative it would be to have an option that could target and convert methionine, lowering total homocysteine levels in the safe and convenient way that SYNB1353 could provide. Ginkgo has been an important part of this program’s journey and the collaboration that has helped us reach the point of studying this new drug candidate in patients.”

 

Revolutionizing Enzyme Engineering: The Synergy of Big Data and AI at Ginkgo Bioworks

Interested in leveraging Ginkgo Enzyme Services for your R&D? Get in touch here

Enzyme Engineering and Artificial Intelligence: A New Frontier

Enzymes are the heroes of biotechnology, serving as biological catalysts that make life’s complex reactions look easy. Inside of the cell, enzymes direct the flow of molecules through metabolic pathways, orchestrating biological functions. Outside of their cellular context, enzymes have been co-opted for specialized roles in manufacturing, speeding up processes that would otherwise be painstakingly slow. In pharmaceuticals, enzymes are custom-engineered to act as targeted therapeutics. Whether in life sciences or industrial applications, enzymes elevate our ability to engineer processes and enact chemistries by facilitating reactions with speed and specificity.

For years, scientists have used a variety of tools to design and optimize these crucial biological components. Traditional methods have often hinged on exploiting evolutionary pressures—letting nature do the heavy lifting over generations and then picking the winners. Structure-based prediction techniques, like Rosetta, also made a significant impact, allowing researchers to model how tweaks to an enzyme’s structure could influence its activity.

But we’re entering a new era–one in which we can train Artificial Intelligence (AI) models based on large biological data sets. This is where Ginkgo Bioworks comes in. Our expansive cell engineering platform is a data-generating powerhouse, churning out the kind of high-quality, voluminous data that AI algorithms thrive on. The marriage of this large-scale data generation with AI models allows us to transcend previous limitations, making Ginkgo an ideal environment to train and deploy machine learning tools for the complex art of enzyme engineering.

The AI Story: Big Data, Bigger Breakthroughs

AI learns from large data sets. Ginkgo Bioworks generates these types of data: we make it possible for you to produce and learn from large data sets. Our extensive repositories of enzymes not only cover a wide range of protein sequences but are also complemented by highly targeted data, revealing precise sequence-function correlations. This dual-data approach is implemented through machine learning cycles in our enzyme engineering projects, enabling us to iteratively refine predictive models.

Ginkgo has developed an AI tool, Owl, to fine-tune enzymes for a specialized role. An expansive data set provides the foundational architecture. To construct the intricate details, however, we employ data that is calibrated to the specific enzyme and its intended function. This enables Owl, our machine learning tool, to not merely “learn” but to “apply” its learnings, writing the intricate, detailed novel enzyme that our scientists require. Owl can “see in the dark” and discern viable paths in complex enzyme design landscapes.

Ginkgo’s approach to enzyme design isn’t merely data accumulation; it’s strategic data deployment. Our Foundry is equipped to generate an extensive range of high-quality biological data at scale. From DNA design and synthesis to high-throughput screening, we create vast data sets corroborating structure-function relationships. Owl thrives in this environment, allowing us to design enzyme variants tailored to our partners’ unique specifications, whether that’s enzyme activity, specificity, or other parameters.

As we navigate the complexities of enzyme design and optimization, think of Owl as the expert navigator and our robust data sets and data-generating capabilities as the compass and map. Together, they form a symbiotic alliance that not only challenges but also redefines the boundaries of traditional R&D.

Tackling Enzymes in Central Carbon Metabolism: the power of iteration and integration

Enzymes that regulate flux through Central Carbon Metabolism (CCM) are biological masterpieces. These proteins have been shaped by billions of years of evolutionary refinement to execute their functions with unmatched precision and, in many cases, maintain high sequence and structure conservation throughout the tree of life.

In one example of Owl-guided enzyme optimization, we were asked to improve the reaction kinetics of an enzyme involved in CCM. While this enzyme had been studied for the past 50 years, the best improvement we found in the literature was a 2-fold increase in the kcat/KM–catalytic efficiency; our customer needed a 10-fold improvement in the efficiency of this enzyme in order to meet their economic targets.

Our approach to this project leveraged our Foundry’s ability to generate and test large libraries of strains. In our initial data-generation phase, we created a first-generation library featuring 2,000 distinct enzyme variants crafted using a structure-based design, as well as semi-rational methods like active-site mutagenesis for targeted alterations. This is an important step because it generated a data set for initial Owl training. With this information in hand, we designed a second generation library to give Owl more information: we maintained the library size of the first but incorporated insights from the previous round, resulting in an exciting 3.9-fold improvement—a leap that surpassed anything we had seen before.

But the real improvements were just beginning. The third generation of this program brought us to a pivotal point in our optimization journey. Leveraging Owl’s predictive analytics, we strategically developed a broad library of 4,000 enzyme variants, generating diversity where it mattered most. The result was an unprecedented 4.5-fold improvement in enzyme efficiency, serving as a testament to Owl’s growing mastery in predictive capability.

Data from these three consecutive generations positioned us to make our biggest improvements yet. Given the data that our scientists had generated, Owl continued to generate increasingly sophisticated models of enzyme function. The final iteration culminated in a fourth generation where only 100 enzyme variants needed to be tested. The result, which marked the successful completion of this customer program, was astonishing: a 10-fold improvement in enzyme function, verified through meticulous arrayed activity assays and detailed protein characterization. By integrating the large data sets generated by Ginkgo’s cell engineering platform with Owl’s predictive power, we surpassed the bounds of natural evolution and decades of research reported in the literature meet our customer’s targets.

The future of enzyme engineering: large data and machine learning at Ginkgo Bioworks

The confluence of big data and AI accelerates the pace of innovation to unprecedented speeds. Ginkgo’s cell engineering platform is an ecosystem designed for generating expansive, high-quality data sets customized for complex biological inquiries. This data, in turn, fuels the predictive power of AI models. Together, they form a symbiotic relationship that enables us to challenge the limitations of natural evolution and traditional research methods.

As stakeholders in the biotechnology industry, navigating complex R&D challenges requires more than just robust tools; it requires effective partnerships. Ginkgo Bioworks offers the specialized machine learning models and data-generation capabilities necessary to advance your research and overcome bottlenecks. Our suite of resources is designed to integrate seamlessly with your objectives, providing actionable insights and solutions tailored to your specific challenges.

Ginkgo is investing in the future of AI for biotech: see our recent announcement with Google about developing foundation generative AI models for DNA and protein. Leverage our expertise and technology for your next project, and to join us in pushing the boundaries of what is possible in synthetic biology.

Developing Enzyme for Single-Cell Library Prep Technology with Factorial Biotechnologies

We’re thrilled to announce our new collaboration with Factorial Biotechnologies, an emerging single-cell sequencing company with a novel intracellular library preparation technology.

Through this partnership, Factorial will leverage Ginkgo Enzyme Services to develop a novel isothermal DNA polymerase for use in their single-cell next-generation sequencing (NGS) library prep kit. Given our extensive expertise in this space, Ginkgo will provide these services under our success-based pricing model, created to help companies de-risk their research and development efforts.

Single-cell sequencing is a promising technique to better understand genetic and functional diversity within complex tissues and biological systems, but its impact has been limited, due to complex laboratory workflows and high cost.

Factorial Biotechnologies aims to dramatically simplify the workflow of single-cell sequencing with an extraction-free technology that makes it possible for complete NGS libraries to be prepared inside of intact cells within a mixed cell population. The potential for this scalable, high-throughput, and cost-efficient technology spans scientific research in the healthcare and life science industries, including precision oncology, immunology, cell and gene therapy, and quality control and screening for synthetic biology. With Factorial’s in-cell library prep technology and barcoding scheme, single-cell libraries can also be prepared using digital PCR workflows.

To support this promising technology, Ginkgo will lead a campaign in P. pastoris to develop a novel enzyme — isothermal DNA polymerase —  instrumental to Factorial’s innovative NGS library prep kit. Our advanced ultra high throughput screening methods can help identify unique enzymes and valuable reagents with desired activity and functions for innovative life science tools and research. Performing discovery and high throughput screening in our proprietary P. pastoris expression system enables synergy between early innovation and manufacturability of these valuable reagents.

“We look forward to working with Ginkgo to develop and optimize a unique and important piece of our workflow. We’re eager to see our cost-effective, high throughput technology help researchers and clinicians deliver on the promise of single-cell genomics.”

John Wells, Co-Founder and CEO of Factorial Biotechnologies

We are so excited to power Factorial’s differentiated technology on our platform. We believe Factorial’s extraction-free library prep will be a game-changer for single-cell sequencing, and we’re proud to help play a part in it. Ginkgo Enzyme Services is uniquely suited to rapidly enable novel molecular diagnostic assays through broad metagenomic searches and efficient AI-enabled enzyme engineering.

Enzymes power a diverse array of applications across industries from industrial processing, chemical manufacturing, therapeutics, as well as applications such as Factorial’s innovation in life sciences and molecular diagnostics. Ginkgo’s platform enables discovery and development of enzymes to enable innovators across industries who seek to make better technologies more accessible.

To learn more about Ginkgo Enzyme Services and how you can access Ginkgo’s success-based pricing, please visit ginkgobioworks.com/enzyme-services/.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

Enhancing Premium Distilled Alcoholic Beverages with Voodoo Scientific

Today, we’re announcing our new partnership with Voodoo Scientific!

Voodoo plans to leverage Ginkgo Enzyme Services to help produce a component of ultra-premium spirit products that are truly smooth.

Most distilled alcoholic beverages produce some degree of harsh sensation, or “bite,” when consumed, which is a major deterrent for many potential customers. Voodoo identified the scientific cause for this harshness and created an enzymatic solution to give distillers the ability to manage it. Distillers can use Voodoo’s novel enzymatic solution to produce more premium products by creating smooth spirits.

Our extensive protein discovery and design capabilities will be used to help develop and optimize the enzyme critical to Voodoo’s product for a wide range of conditions in spirits manufacturing, from craft to global-scale production environments.

“Providing distillers with a means to eliminate, or control, the harshness of their spirits products is very gratifying,” said Joana Montenegro, co-founder and Chief Science Officer at Voodoo. “We believe we can enable new innovation in this large global industry and in ways that are truly meaningful to consumers seeking premium experiences. Ginkgo was the best choice of partners for us among the ones we considered because of their unique combination of strong scientific capabilities and a business model that fits an early-stage company like ours.”

Engineering this class of enzyme to operate under the unique conditions required for distilled alcoholic beverages is a great application for Ginkgo Enzyme Services. Improving the functionality of enzymes underpinning critical production processes – making enzymes work better – is an area we’re passionate about because it opens up real business opportunities for our customers, especially as they push into new product development.

To learn more about Ginkgo’s work in this space, join us on June 30th from 10:00 – 11:00 am ET for our Functional Food Proteins with Microbial Expression Systems virtual event.

What will you grow with Ginkgo?

Sustainable Innovation in Generic API Space with Centrient

Reducing the Environmental Footprint of Enzymatic Production of APIs

Today we’re pleased to announce an expansion of our existing partnership with Centrient, the global business-to-business leader in sustainable antibiotics, next-generation statins and anti-fungals. The partnership is aimed at broadening Centrient’s portfolio of environmentally friendly active pharmaceutical ingredients (APIs), following the success of previous work together.

Our ongoing partnership with Centrient focuses on improving the sustainability of fermentation and enzymatic syntheses of beta-lactam antibiotic APIs. In the first phase of this project, we delivered an enzyme with significantly improved efficiency, reducing the environmental footprint of enzymatic production of amoxicillin and cephalexin APIs. These semi-synthetic beta-lactam antibiotics are widely prescribed to both children and adults and are on the World Health Organization’s List of Essential Medicines. Centrient aims to build on these improvements through ongoing strain projects on our platform which focus on reducing carbon emissions and waste production compared to traditional chemical routes.

Our Ginkgo Enzyme Services are enabling Centrient’s sustainable API production

“Our partnership with Ginkgo is fully aligned with our main purpose: to improve lives through innovative and sustainable manufacturing of medicines,” said Jorge Gil-Martinez, Chief Scientific Officer at Centrient. “The initial success of this collaboration has led us to expand our joint efforts to design new ways of producing essential medicines, minimizing the environmental impact of antibiotic manufacturing. Moreover, as we design and execute our Open Innovation business model, this strategic collaboration creates synergies to accelerate the diversification of our portfolio, a strategic pillar for the future of our company. Access to external disruptive technologies, focusing on enzymes and fermentation, contributes to our vision to be a diversified and integrated partner of choice for generic medicines.”

Our partnership with Centrient, which began in 2021, underscores Ginkgo’s commitment to supporting biopharma companies in bringing much-needed innovation to the field. We are inspired by the early success we’ve already seen in our partnership and look forward to expanding our joint efforts to ultimately support better patient outcomes.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

Optimizing Enzyme Expression and Performance with Zymtronix

Optimizing enzymes for Zymtronix’s cell-free manufacturing platform

Today we are pleased to announce our partnership with Zymtronix, a developer of cell-free process technologies. Together we aim to optimize enzymes used in Zymtronix’s proprietary cell-free platform for the production of important ingredients in food, agriculture, cosmetics and pharmaceuticals.

Enzymatic biocatalysis is a powerful manufacturing technology that can enable the production of a wide range of chemicals and molecules. Zymtronix’s cell-free platform is designed to solve challenges associated with traditional biocatalysis and seeks to enable the production of a wide range of products with precision and productivity. By partnering with us to build and produce bioengineered market-ready enzymes, Zymtronix anticipates being able to extend its solutions into the pharma, nutrition, agriculture markets, among others.

Zymtronix aims to leverage Ginkgo Enzyme Services to discover, optimize, and produce enzymes

Ginkgo Enzyme Services offers partners end-to-end support for the discovery, optimization, and production of enzymes for diverse applications. Through the partnership, we will leverage our suite of enzyme services to engineer enzymes for Zymtronix’s applications using metagenomic enzyme discovery as well as improve enzyme expression and production host performance.

We’re thrilled to welcome Zymtronix to the platform and support their applications in sustainable ingredients and beyond. We’ve built out our platform to serve a wide variety of enzyme discovery, engineering, optimization and scale up efforts, and we’re so excited for the work to come in this partnership. Zymtronix’s cell-free biomanufacturing platform is pioneering solutions for various industries, and we’re eager to leverage our end-to-end capabilities and help expand its efforts in transforming the way enzymes are used.

“This partnership will greatly accelerate our work of bringing the precision and scalability of cell-free biomanufacturing and sustainable ingredients to market starting with alternatives to animal sources; Ginkgo is uniquely able to support us with both enzyme engineering and strain expression, helping us continue to accelerate commercialization,” said Stéphane Corgié, CEO-CTO and founder, Zymtronix. “We hope to extend this partnership in the future to facilitate the production of multiple end-market products.”

To learn more about Ginkgo Enzyme Services, please visit ginkgobioworks.com/enzyme-services/.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

The Enzyme Intelligence Virtual Event

Enzymes are having a moment

These days, there’s a lot going on in the enzyme space. Machine learning (ML) is changing the way we think about the previously hard problems of modeling protein structures and predicting protein functions. Enzyme-driven industries like pharmaceutical manufacturing, diagnostics, and industrial green chemistry are looking forward to new and better enzymes made possible by ML.

At Ginkgo, we love technologies that make biology easier to engineer. We’ve built an ML-guided enzyme engineering stack that draws on our Foundry’s established strengths in assembling smart DNA libraries, engineering organisms, and screening in (ultra) high throughput. The result is the new Ginkgo Enzyme Services offering that enables our customers to discover new enzymes and optimize existing ones. We’re super excited to share the results being delivered.

So let’s take a moment to talk about enzymes

On December 15th, Ginkgo hosted the Enzyme Intelligence Virtual Event. Dr. Emily Wrenbeck, Head of Protein Engineering, presented to an audience of more than 450 about how Ginkgo’s Foundry combines ML with massive experimental datasets to enable enzyme engineering.

The presentation was structured around 4 case studies:

  • Enzyme Discovery. An ML-guided search of a large metagenomic library led Ginkgo to an unexpected corner of sequence space, producing dozens of candidate enzymes and opening up IP options for the customer.
  • Better Activity. A customer’s project-critical enzyme had a reputation for being recalcitrant to engineering. Iterative protein design cycles produced a 10-fold improvement in activity over wild type as measured by kcat/KM.
  • Better Specificity. A naturally sourced enzyme made 4 undesired byproducts, with the desired product only 10% of the total. Ginkgo tested over 10,000 variants with ultra high throughput GC-MS to bring the product specificity to over 75%
  • Better Biocatalysts. A customer’s enzyme suffered from a low S:H (synthesis:hydrolysis) ratio. In a single round of engineering, Ginkgo was able to improve both enzyme speed and specificity under industrially relevant process conditions.

A recurring theme in the event was the value added by integrating ML tools with the broader capabilities of Ginkgo’s foundry. An engineering cycle that brings together DNA assembly, assay development, high-throughput screening, computational tools, and human experts is required to consistently deliver improved enzyme performance.

Far from replacing data, ML makes data more valuable. The massive biological datasets Ginkgo can generate were key to the success of these enzyme engineering programs.

It’s time for end-to-end Enzyme Services

Following the technical presentation, Ginkgo’s Business Development team took the stage to answer questions about Ginkgo’s latest offering. Building on powerful ML-guided enzyme engineering capabilities, Gingko Enzyme Services offers end-to-end solutions for R&D leaders looking for better enzymes.

  • Novel Enzyme Discovery. Ginkgo’s large in-house metagenomic libraries are combined with ultra high throughput screening to identify new enzymes with a desired activity. These enzymes are often unrelated to previously described candidates, opening up new IP options for customers.
  • Function & Stability Optimization. ML-guided protein design is combined with a range of sequence-based, structure-based, and classical enzymology tools to improve a candidate enzyme’s activity, stability, specificity or expression level.
  • Robust Host Strains. Ginkgo customers have access to proprietary bacterial and fungal host strains optimized for protein production, including methanol-free Pichia pastoris and low viscosity Aspergillus niger.
  • Fermentation Process Development. When it comes to commercial-scale enzyme production, Ginkgo offers automated DOE (Design of Experiments) in Ambr® 250 bioreactors to optimize the production process.
  • Manufacturing Scale-Up & Tech Transfer. Ginkgo can perform pilot-scale fermentation up to 3,000 L. Customers are supported in the development of downstream processing and purification methods. Ginkgo can transfer processes to a manufacturing partner, including for GMP production.

Make the most of this moment for enzymes

A key theme of the Enzyme Services portion of the event was the flexibility of Ginkgo’s offering. As a horizontal platform, Ginkgo supports customers through the entire enzyme R&D process from discovery to development and deployment. This versatility is essential to serve the diverse needs of customers across a range of enzyme-powered industries including: animal feed, biocatalysis, diagnostics, green chemistry, metabolic engineering, mRNA manufacturing, waste remediation, and more!

A recording of the Enzyme Intelligence Virtual Event is available here. Ready to engage Ginkgo’s Foundry for your project? Have questions? Contact [email protected]

What will you grow with Ginkgo?

Launching Ginkgo Enzyme Services

Enzyme Services to Enable Applications across Pharmaceuticals and Diagnostics, Food and Agriculture, and Beyond

Today we are very pleased to announce the launch of Ginkgo Enzyme Services. Ginkgo Enzyme Services is powered by ultra high throughput screening and machine learning-guided protein design, as well as optimized proprietary bacterial and fungal host strains. Ginkgo Enzyme Services solves challenges for R&D teams developing enzymes, from discovery of novel enzyme activity through optimization of enzyme function and large scale manufacturing.

A virtual event on Dec. 15 will give an overview of Ginkgo’s Enzyme Intelligence approach to machine learning-guided enzyme engineering

Enzymes are valuable biocatalysts used across a wide range of industries including in the production of medicines, food, materials, and beyond. Our end-to-end Enzyme Services support R&D leaders looking to identify new enzyme activity to replace existing chemical synthesis steps, improve enzyme specificity, activity, and stability in industrially relevant conditions, and optimize the manufacturing of enzymes for reduced cost of goods and environmental impact.

We’ve supported enzyme R&D programs across a wide range of industries, including biopharma manufacturing and discovery. Notable enzyme services projects include breakthrough work with Aldevron to improve the manufacturing efficiency of vaccinia capping enzyme, a critical reagent used in the production of mRNA vaccines, and a recently announced partnership with Merck to develop biocatalysts for active pharmaceutical ingredient (API) manufacturing.

Our suite of services covers the full end-to-end process for enzyme R&D, providing synergies between enzyme sequence, host strain, and manufacturing processes that can enable commercial success.

Ginkgo Enzyme Services includes:

  • Novel Enzyme Discovery
  • Enzyme Function & Stability Optimization
  • Access to Optimized Host Strains for Robust Expression
  • Optimized Fermentation Process Development
  • Manufacturing Scale-Up, Process Development & Tech Transfer

“Most R&D teams working on developing enzymes expect to need to stitch together a bunch of different services and tools, both in-house and external to make their enzymes work,” said Jake Janey, PhD, a pioneer in the field of biocatalysis. “The ability for Ginkgo to guide the process all the way, providing many intermediate touchpoints with data and prototypes for development and decision making, is a great value-add.”

At Ginkgo, we are constantly working to improve our platform to provide best-in-class services to enable our customers to meet their R&D challenges head on. As a horizontal platform, we have the flexibility, breadth, and scale to serve customers across biocatalysis, diagnostics, and beyond with the full spectrum of tools they need to discover, develop, and deploy enzymes for their processes and products.

With world class expression hosts, automation, computational design, and fermentation capabilities, we are excited to partner with companies across all industries to bring their enzyme-dependent products from conception to market more swiftly and reliably than ever before.

Virtual event details:

Join us for Enzyme Intelligence, a virtual event featuring Ginkgo’s head of protein engineering, Emily Wrenbeck, on December 15, 2022. Sign up here.

Learn more about Ginkgo Enzyme Services at our webpage, or write to us at [email protected].

Find the full press release here along with all of the latest news from the Ginkgo team.

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