In her current publication, Diana Amariei describes the successful optimisation of the C-methyltransferase PsmD, which is involved in the biosynthesis of physostigmine, a well-known AChE inhibitor.
Through iterative saturation mutagenesis, she succeeded in enlarging the catalytic centre of PsmD and increasing the enzyme activity towards bulky, non-natural substrates without impairing stereoselectivity. An automated method for expression and screening of the generated enzyme variants (as part of the AutoBioTech-project) enabled the identification of several mutants with increased specific activity. Particularly noteworthy is the mutant W166C, which was successfully used for the preparative synthesis of an AChE inhibitor.
We congratulate Diana and her cooperation partners from the research centre and Heinrich Heine University on this outstanding publication.