Researchers Develop Enzyme to Convert Various Biomaterials Into Biodegradable Plastics

The enzymes to be developed in this research project will have levels of toughness and ductility similar to those of the plastics currently dominating the market. However, these new bioplastics—polyhydroxyalkanoates (PHA)—will be produced using domestic raw materials such as corn, sugar, or agricultural waste, instead of relying on petroleum-based chemicals.

“Nearly 99% of the plastic produced today is made from petrochemical products extracted from oil or natural gas, which usually have to be imported from outside the United States."Sankaranarayanan said."We hope to utilize locally available materials, such as those commonly used in Indiana.

Moreover, Sankaranarayanan claims that they can be infinitely recycled while retaining their mechanical strength.

“You can break these polymers down into individual units and then reuse them over and over again."Sankaranarayanan said."PHA was discovered nearly a century ago, but its potential brittleness and instability at high temperatures have hindered its widespread use in consumer goods or medical devices. Our platform will be able to tailor the chemical structure of the final polymer to achieve appropriate levels of mechanical strength and thermal stability. This will open the door to a wide range of applications, from packaging to biomedical devices.

The main focus of this three-year project is biocatalysis—using enzymes to accelerate highly specific reactions to produce desired products without harsh chemicals or extreme conditions. Biocatalysis makes biomanufacturing a more sustainable and efficient alternative to traditional chemical manufacturing. Creating computational tools to identify opportunities for biocatalysis is key to unlocking its potential.

Researchers at Purdue University are developing algorithms to select the enzymes and reactions required to produce bioplastics. Then, researchers at the University of California, San Francisco (UCSF) will use advanced protein computational design methods to design these enzymes, leveraging deep learning, a machine learning technique that mimics the brain's pattern recognition.

Once the enzymes are designed, they will be sent to researchers at Stanford University to test their functionality, and then to Purdue University, where researchers will analyze their reaction rates and their ability to modify polymer chemical structures. Finally, researchers at the University of California, Berkeley will determine their properties and commercial potential, as well as how to engineer microorganisms to scale up biomanufacturing.

Sankaranarayanan listed the identification of adaptable enzymes as one of the main challenges related to the project.

“The enzyme we are using, polyketide synthase (PKS), is a complex enzyme capable of catalyzing consecutive chemical reactions in an assembly line manner to produce complex antibiotics."Sankaranarayanan said."However, they are not designed to work in the industrial processes of producing bioplastics. Therefore, we are trying to figure out how to alter their natural chemical reactions to produce the desired bioplastics while enhancing the stability of engineered enzymes to enable large-scale biomanufacturing.

Another challenge of using these enzymes in a manufacturing environment is their DNA composition. PKS contains a high content of guanine and cytosine—two of the four bases that carry genetic information in DNA—which poses a significant challenge for DNA synthesis in subsequent enzyme production. Another partner in the project, Twist Bioscience, has developed this technology, allowing researchers to design the necessary enzymes.

Emily Leproust, CEO and co-founder of Twist Biosciences, said:Collaboration with Purdue University has elucidated the practical applications of complex sequences, enabling Twist to further enhance our ability to manufacture challenging and previously difficult-to-synthesize sequences at scale, turning what was once considered difficult into routine.。“This project provides a strong example of how innovation and partnerships can expand the boundaries of discovery for a variety of real-world applications.

In addition to the team's contributions to biomanufacturing, they will also provide research opportunities for students and resources for the broader scientific community. Three graduate students have already been hired for the project, and researchers will recruit undergraduates in the fields of agricultural and biological engineering, computer science, chemistry, and chemical engineering.

Sankaranarayanan stated that they will also provide open-source access to all their tools and workflows, as they can be applied to pharmaceuticals, agrochemicals, pesticides, or herbicides, and even other types of biomaterials such as rubber with only minor adjustments. They will also develop a protein design workshop led by the University of California, San Francisco, with Purdue University providing modules on designing step-by-step enzyme processes.

“One thing I really like about this grant is that we have researchers, postdocs, and graduate students from all these different universities, each bringing their own unique strengths.Sankaranarayanan said.Therefore, students at Purdue University have the opportunity to interact with some other faculty members and their lab members, which is very exciting.

This project is funded by the NSF Directorate for Technology, Innovation and Partnerships through the Use-Inspired Acceleration of Protein Design program.