A team from Groningen and Barcelona cleared up what takes place when you put a designer enzyme with unnatural amino acids through a directed evolution campaign, as shown in ACS Catalysis. ‘We didn’t anticipate this at all.’

Enzymes are magnificent catalysts, but they are usually also hyper specific, meaning they can do one chemical transformation extremely well. This also comes into play when designing new enzymes. ‘Another limitation is that there’s only so many reactions you can do with natural enzymes’, says Reuben Leveson-Gower Assistant Professor at TU Delft. ‘In the lab of Gerard Roelfes – where I did my PhD – they initiated an interesting strategy to expand the reactions.’ Roelfes’s group uses unnatural amino acids in their enzyme designs. ‘Encoding these gives new chemical functions.’

During his PhD, Leveson-Gower used para-aminophenylalanine (pAF) to imitate organocatalysts. ‘Organocatalysis is very useful for chemical syntheses and of course won the Nobel Prize in 2021. This type of chemistry could be really powerful and efficient if done in an enzyme, and that’s exactly what we accomplished.’