Bacteria are incredibly chemically diverse: there are bacteria that breathe metals, make their own fertiliser from the air, eat electricity, and that can convert gaseous carbon dioxide into useful chemicals without the need for photosynthesis. Unfortunately, many of the bacteria that have useful chemical properties are hard to grow, grow sluggishly, or are so fastidious that we don’t even know how to grow them in the lab.
On the other hand there are tame bacteria, like Escherichia coli, that we understand at a molecular level and will happily and rapidly grow on inexpensive nutrient sources. Ideally, we would be able to take interesting chemical properties from hard-to-grow bacteria and transplant them into laboratory stalwarts, such as E. coli. In a collaborative project between researchers at the CSIRO’s Synthetic Biology Future Science Platform, the Australian National University, and the University of Auckland in New Zealand, we’ve done just that by moving the synthetic pathway for exotic cofactor F420 into E. coli.
Cofactor F420 is a small molecule that has pivotal roles in some important biological processes, such as the conversion of carbon dioxide to methane, the breakdown of explosives (such as TNT) in the soil, and the production of some antibiotics. The team took the genes needed for the biosynthesis of cofactor F420 from different bacteria, reassembled the biochemical pathway in a laboratory strain of E. coli, and then showed that their new E. coli strain not only made cofactor F420, but could use it to conduct chemical transformations.
The research also revealed that our understanding of cofactor F420 was flawed. The textbook explanation for one of the steps in cofactor F420 production needed a chemical that E. coli doesn’t produce (2-phospholactate). The team’s work showed that this chemical was not needed at all, but instead cofactor F420 production uses a chemical that is abundant in E. coli and other organisms (phosphoenol pyruvate). This revision provided the insight that enabled the production of the cofactor F420 producing E. coli strain.
It’s hoped that the new E. coli strain is the first step towards microbial factories that can exploit the unique properties of cofactor F420 for the sustainable production of chemicals that we currently produce from non-renewable sources.