Nearly 40 years ago, scientists at Genencor, a part of IFF today, had a radical vision for using biotech techniques to build better enzymes for laundry detergents.
Most in the industry thought their approach was impossible—a fool’s errand.
The consensus was that enzymes pulled from nature couldn’t be improved upon. “The belief was that you’re sort of stuck with what nature makes, and that was it,” says Dave Estell, a founding Genencor scientist, fellow, and laureate at IFF today. “There was no way to make it any better, and if you could do it, you couldn’t do it at a reasonable cost at industrial scale.”
In the 1970s and 80s, the San Francisco Bay area was the fertile crescent of modern biotechnology. Genencor, founded in Palo Alto as a partnership between Genentech and Corning, was the first biotech company to apply these cutting-edge technologies to industrial enzyme production.
But the team of pioneering scientists proved them wrong. The techniques and processes they developed enabled the first successful commercialization of a protein-engineered laundry detergent enzyme, laying the groundwork for a whole new category of biotech products.
Today, these experts, who are now a part of IFF, continue to lead this bio-revolution. By harnessing the power of enzymes—an abundant natural material—IFF’s scientists are innovating to develop and manufacture complex, sustainable ingredients. These solutions not only reduce our dependence on fossil fuels, but also deliver exceptional performance.
“We’re applying science and technology to go after generational challenges, environmental challenges, and the things that drive our customers forward into the future.”
Scott Power
IFF fellow and early Genencor employee
Photo below: the early lab team who developed the first protease for laundry detergents
The birth of modern industrial biotechnology
Genencor’s scientists got their first opportunity to showcase their protein engineering expertise in 1983, when Procter & Gamble approached them about needing a better protease (an enzyme that breaks down protein-based stains) for its liquid formula. Enzymes in their natural form had already been used in granular detergent formulas for some time, but when added to liquid formulas, they’d become unstable, quickly degrading and losing their catalytic activity.
To engineer a better protease, Genencor’s scientists set out to tweak the protein’s structure to improve its function.
Every protein including enzymes is made up of a long chain of amino acids— like a string of beads.
There are 20 different types of amino acids.
By changing its amino acid sequence—or the order of beads on the string—scientists can alter the shape and function of the enzyme to deliver desired properties for laundry detergent applications.
After months of iterative testing, scientists landed on the precise single genetic mutation that would change the protease’s amino acid sequence to make it more stable and more active. This groundbreaking discovery enabled enzymes to be used in a liquid laundry formula for the first time ever—helping to improve the cleaning performance of products like liquid Tide®, a best-in-class laundry detergent that has been used by millions around the globe.
Masters of Scale
From these early days, the team of industrial enzyme pioneers has continued to evolve and expand—first being acquired by Danisco, then DuPont, and then merging to become Dow and DuPont.
And most recently, in 2021, IFF acquired DuPont’s Nutrition & Biosciences division, expanding the enzyme experts’ global footprint and capabilities.
With each successive company change, the enzyme leaders have continued to build upon this collective knowledge in their tools, host organisms, and scientific expertise.
While many companies can do protein engineering today, IFF has been the “master of scale.”
Enzyme development is a complex and costly process. Translating an optimized protein developed in a lab into a commercial product requires many layers of expertise. And unlike smaller companies, which often specialize in one approach, IFF has a diversity of biotech tools to draw from to select the best strategy to tackle a challenge.
Combining these strengths, IFF has a proven track record of engineering for multiple customer needs: scalability, manufacturability, functionality, and the environment.
Biology with Intention
In recent years, major technological advances from high-throughput screening to AI and CRISPR/Cas9 have made enzyme development faster and resulted in more effective products. But human talent is still the “secret ingredient” required to unlock the potential of these technologies. To that end, IFF has built consensus-driven, fully integrated teams, bringing together experts in high-tech computing, analytical chemistry, molecular biology, and industrial production.
At the core of IFF’s approach to enzyme engineering today is a powerful technique known as directed evolution. This Nobel Prize-winning technique helps guide biology to create enzymes that have desired properties, such as cleaning at colder temperatures or targeting specific stains.
To start any project, IFF’s scientists select a natural enzyme from their extensive library. Then, using advanced high-throughput screening tools, they can screen thousands of variants at a time to narrow down the finalists that will go on for further testing and development.
But before screening can even begin, the most critical step is to develop the right set of assays, or screening tests, that can efficiently identify the new enzyme candidate.
“There's a real art to developing an assay that is screenable, and that we can downscale, and we're really good at that. For example, if a customer says they want a better performing protease, what they really may need is a more stable enzyme. We really understand the application, and we consider the way the enzyme performs, during the whole washing cycle, and then translate that into our high-throughput assays.”
The assays are performed in microtiter plates containing rows of small wells, each mimicking the conditions of a tiny “washing machine.”
Inside each well is an enzyme variant mixed with detergent, and a swatch of cloth with a specific stain. The scientists can track these experiments in real time thanks to end-to-end databases and barcoding technology.
“We have the benefit of seeing data popping up in real time. And trying to pick out which mutations in these variations are beneficial or not,” adds Pricelius. Scientists can spend up to six months iteratively testing and refining enzyme candidates in order to identify the winning candidate.
AI-Designed Enzymes
In parallel to these lab experiments, IFF’s scientists are also using AI to further push the boundaries of enzyme development. Similar to consumer tools like ChatGPT that use data from written language to generate text, these AI models are trained on data obtained from proteins to predict enzyme activity. These tools can propose thousands of new enzyme variants that IFF scientists may not have found using traditional screening and selection methods.
“It's an exciting opportunity. Protein engineering today has ultimately become a data science challenge. But AI tools alone won't get us there. You have to understand both worlds, the computer sciences and the life sciences, to ask the right questions and to understand the data. You need to keep in constant contact with experimental scientists. You could have generated an enzyme that is superactive, but don't know how well it expresses from an industrial point of view.”
Advancing the Bioeconomy
As signs of global warming only increase each year, and consumers, regulators, and other stakeholders demand more sustainable products, IFF is uniquely suited to meet this critical moment. With over 40 years of experience in industrial biotech, IFF has the unique capabilities to lead us to safer and more sustainable innovation.
IFF is already taking a lead in the U.S. bioeconomy.
Last September, President Biden issued an executive order to accelerate biotechnology innovation. As a part of these ongoing efforts, IFF’s Luis Cascão Pereira, Global R&D Ventures Lead, was invited to a White House session to share his perspective on using biomanufacturing to strengthen the U.S. supply chain. “I was able to make solid recommendations based on real-world experience that I’ve gained over the course of my career in biosciences,” says Pereira.
Following the event, Pereira was also asked to consult on developing policy frameworks related to these new initiatives.
For IFF scientists, optimized enzymes for laundry and dish detergents are just the start of our bio-based future. “We’re just at the very, very beginning,” says Redestig. “And I think there are a lot of answers to reducing our dependence on fossil fuels, to our ailments, to our consumer needs, that live in the better use of enzymes and proteins.”
PART TWO:
Enzyme Innovation for Performance and Planet
Learn how protein engineering impacts both performance and sustainability, the next story in our series exploring IFF's biotech origins and innovations in Home and Personal Care.
