Our goal
Mevalonate is a pre-cursor to many isoprenoids. To provide a strong node to build additional, more-complex products from, we focused on building a highly efficient mevalonate microbe. We set ourselves the challenge to do this in just eight weeks, demonstrating the speed of our bio:drive and grow:bot tools.
How did we do it?
We started with our bio:drive tool. bio:drive found biochemical pathways from the central metabolism of E.coli to mevalonate, selected 13 enzymes to investigate across three biochemical reactions, and designed four host microbe optimisations to improve pathway flux.
With variations in enzyme choices, expression levels and host microbe edits, this resulted in over one million microbe designs. After a sense-check from our twiglet scientists, these microbes were ready to be built in the lab with grow:bot. The entire design process took us just a few hours.
grow:bot is our automated lab. Every scientific step has been designed to optimise automation, limiting errors and allowing our scientists to focus on the meaningful parts of scientific discovery. The process is standardised, meaning every microbe at twig is built in exactly the same way.
The grow:bot process also has one key feature. It is a forcing funnel, at each stage using analytics to only progress the best microbes and cut out the rest, saving both time and money.
The result
In just eight weeks we progressed from over a million microbe designs to a shortlist of 25 top-performers, all producing mevalonate. Our best microbe was 1,600% better than our worst.
A sample of these strains were then taken into our scale-down fermentation array. Our best-performing microbe achieved 59% of the possible maximum theoretical yield, making 0.32g of mevalonate for every gram of glucose, matching similar results in E.coli.
Using our grow:bot platform, we are able to rapidly build and test microbes, creating a foundation for further improvement using bio:drive.