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AI-powered design tool and BioXp™ system accelerate metabolic engineering

January 27, 2021  |  Codex DNA

The next industrial revolution will be biological. By turning cells into factories, synthetic biology changes how we make everything from plastic to food to medicine. But achieving those goals will require overcoming the limitations of DNA design. This is still a complex, time-intensive task most often done through inefficient trial-and-error techniques.

Without effective DNA design tools, the cost of going from an idea to a testable prototype is preventing exploration in the field. That’s where Doulix comes in. Based on the concept of empowering biologists to realize the full potential of forward engineering, Doulix offers AI-powered, computer-aided software for streamlined design of optimized, error-free DNA fragments.

In a recent webinar, Doulix CEO Davide De Lucrezia presented a case study about rapid design and manufacturing of complex metabolic pathways using Doulix tools in combination with the BioXp™ system from Codex DNA. The approach is one of rational engineering, he said, helping scientists by radically reducing time to prototype.

De Lucrezia noted that several unique features contribute to Doulix’s powerful approach: a large collection of in vivo characterized standard DNA parts; a proprietary DNA editor that works with many different levels of complexity; and an AI-driven synthesis wizard. Together, these make it possible to quickly pull together pre-made DNA parts into new pathways.

While conventional design software requires that users input the exact fragments to be assembled, De Lucrezia said, the AI-powered Doulix algorithm can be used to automate synthesis fragment design for metabolic pathway assembly, and to automatically eliminate design options that are predicted to function poorly but would otherwise require expensive synthesis and screening. He offered several examples of how this refactoring approach led to improved production of desired components in engineered microbes.

De Lucrezia also presented a more detailed look at a project done in collaboration with scientists at the University of Manchester, through the EU-funded TOPCAPI project, in which the goal was to refactor and redeploy a key antibiotic-production pathway in an industrial-friendly microbial host. Doulix was responsible for synthesizing and assembling the metabolic pathway, a task made more complicated by the sequence complexity and extreme GC regions.

This was not the kind of DNA that could be ordered from a standard synthesis vendor, De Lucrezia said. That’s where the BioXp™ system came in. By pairing the BioXp™ instrument’s capabilities with the Doulix design tools, the team was able to perform rapid prototyping of the 35 kb pathway with higher accuracy than standard synthesis and assembly methods. The tremendous effort could not have been undertaken without this advanced workflow.

Interested in learning more? See how the BioXp™ system streamlines metabolic engineering.

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