Characterization of the key enzyme that controls macrolides’ configurations in their biosynthesis

January 9, 2026

Accurate reaction analysis using chemical synthetic substrates

Macrolide antibiotics are a class of polyketides whose bioactivity is strongly dependent on the spatial orientations (configuration) of the functional groups they possess. A group of researchers from Tohoku University and the RIKEN CSRS elucidated the function of the b-ketoreductase (KR) domain, which is the key to controlling the orientations of functional groups in the biosynthesis of pikromycin, a model compound in macrolide biomanufacturing. The research group conducted an experiment using their own synthesized substrates and identified the configuration of the KR domain product that had been unknown before. These findings will help improve the accuracy of predicting products’ configurations from amino acid sequences of the KR domain and enable logical enzyme designing. In the future, these findings are expected to be applied to the production of new-generation materials to create innovative medical compounds that do not occur in nature.

 

Original article

Chemical Science　doi: 10.1039/D5SC07470C

E. Okamura, K. Ohsawa, H. Ban, Y. Sugiyama, J. Hashimoto, K. Kudo, M. Yoshida, K. Shin-ya, H. Ikeda, S. Takahashi,T. Doi,

"Characterization of the ketoreductase domain of pikromycin module 2".

Contact

Shunji Takahashi
Unit Leader
Natural Product Biosynthesis Research Unit