Metabolic engineering automated with PIXL Dark

Rational engineering strategies, based on mechanistic understanding of components, are helpful towards strain improvement. But they are rarely sufficient when used alone.

Recombia’s solution is to complement the specificity and versatility of rational design with the breadth of ‘target-agnostic’ approaches, as Hui Zhou, Head of Metabolic Engineering at Recombia, explains:

“At Recombia, projects usually begin with a rational engineering approach supported by careful techno-economic analysis. We take information from the biochemical and enzyme engineering literature, and from our own experience, and design genetic changes into prototype strains exploring a certain metabolic space. With the help of quantitative scaled-down models of fermentation and system biology, we then study the response space generated by our genetic changes.”

Recombia’s state-of-the-art technologies effectively potentiate donor-templated DNA repair to enable precise multiplexed genome editing. Ensuring the new sequence (the donor DNA) has accurately and efficiently replaced the previous sequence helps generate production-ready strains with the potential to scale almost seamlessly into industrial workflows.

“What we’ve learned from taking this systemic approach is that, of course, biology is complicated and often there are unpredicted consequences to making such changes. Combining rational approaches with either systematic unbiased screening or selection of large libraries of strain variants therefore gives us a much clearer picture of how well strains will perform in manufacturing conditions,” adds Massimo Merighi, Chief Bioengineering Officer for the company.

Bob was one of the early pioneers of ROTOR+, Singer Instruments’ high density arraying robot. Its ability to reformat plates at a rate of nearly 1 million colonies an hour has seen ROTOR+ grow into somewhat of a secret weapon for the bioengineering community.

ROTOR+ helped take the sting out of library construction in the early days. But with the founding of Recombia, and multiple new projects on the horizon, Bob says consolidating those increasingly large collections has rapidly become the next bottleneck:

“We have several very large complex libraries that consist of many clones. We can use next generation sequencing to identify non-redundant sequence validated clones within that set. But what we end up with is potential candidates in the thousands or even tens of thousands.

“So in our Design, Build, Test, Learn cycle, the Test remains the bottleneck of the whole process. And we need to first reduce down the number of clones to a smaller more manageable set to increase feasibility.”