Neochromosome, a biotechnology firm specializing in genome-scale cell engineering and a subsidiary of Opentrons Labworks, has announced a collaboration with Dr. Giovanni Stracquadanio from the University of Edinburgh. The partnership employs artificial intelligence (AI) and machine learning to expedite the development of more robust and novel enzymes, aiming to enhance the engineering processes for designer enzymes. This advancement has the potential to improve the creation of safer and more effective therapeutics, including enzyme replacement therapy, for a diverse range of genetic diseases.

In nature, numerous enzymes exist, but not all possess the potency required for industrial or clinical applications, such as the development of highly efficient and secure therapeutics. Traditional methods involve the creation of libraries of synthetically-generated enzymes, known as 'designer' enzymes, through computational and experimental techniques. However, this approach is time-consuming, and the performance of these designer enzymes often falls short of expectations. In contrast, the utilization of AI and machine learning can enhance the prediction of precise enzyme structures encoded by specific, previously undiscovered DNA sequences.

“Current methods of engineering enzymes are expensive and low throughput, and most designer enzymes lack efficacy. Therefore, there is an urgent need to establish new methods of reliably creating designer enzymes on demand,” said Dr. Leslie Mitchell, Co-founder and CEO of Neochromosome. “This project has enabled Neochromosome to explore a new approach to enzyme engineering, demonstrating the power of our DNA foundry to enable machine learning-directed protein engineering.”

Supported by the Industrial Biotechnology Innovation Centre (IBioIC), the collaboration implemented a workflow for improved enzyme engineering, integrating automation, AI, and biophysics to identify ideal enzyme candidates for experimental screening. Neochromosome utilized its DNA foundry to construct a defined variant library, while Dr. Stracquadanio's lab assessed enzyme production and testing using Opentrons' automated liquid handling robots.

The collaboration resulted in the in silico creation of thousands of different kinase mutations, predicting the free energy of each mutant through a biophysical model. An AI tool was then employed to generate new sequences with predicted low free energy, ultimately leading to the development of 40 novel, designer-engineered enzymes.

“The ability to create designer enzymes by leveraging AI is a significant milestone for the field of synthetic biology, especially for the development of safe and effective treatments for genetic disorders,” said Dr. Giovanni Stracquadanio, Senior Lecturer in Synthetic Biology and Co-director of the Edinburgh Genome Foundry at the University of Edinburgh and Co-founder of ZYTHERA. “We’re excited to continue our partnership with the world-class scientists and bioengineers at Neochromosome and use their impressive platform to generate novel engineered enzymes.”

Neochromosome's DNA foundry and customized flexible workflows enable scientists to scale and streamline biological engineering experiments. From defined variant libraries to clonal selection and DNA repository, Neochromosome collaborates with partners in an iterative, customized process, ensuring high-quality deliverables with rapid turnaround times.