In her current publication, Mona Haase describes the detailed characterisation of the C-methyltransferase SgMT from Streptomyces griseoviridis. This fascinating enzyme class plays a key role in the methylation of the C3-indole of pyrroloindoles, an important structural component of many bioactive natural products.
The use of X-ray crystallography has allowed the three-dimensional structure of SgMT to be elucidated. These findings are invaluable because they enable targeted mutagenesis to further investigate the enzyme. The investigations have brought to light a fascinating network of tyrosine side chains that are involved in the catalytic activity.
These experimental studies were complemented by extensive molecular dynamics simulations and docking experiments. This made it possible to visualise the binding behaviour of the cyclo-(LL)-ditryptophan substrate at the molecular level.
Thanks to this interdisciplinary approach, not only were key mechanisms of enzyme catalysis deciphered, but potential starting points for optimising SgMT as a biocatalyst were also identified.
Particular emphasis should be placed on the excellent cross-institutional collaboration between the scientists of the three participating institutes. Combining their respective core competencies allowed the researchers to gain a comprehensive picture of the catalytic properties of SgMT.
We congratulate everyone involved on this outstanding publication, which provides valuable impetus for the further development of enzymatic methylations in natural product synthesis.
The publication is online available.