Successful generation of Novel Reveromycin Derivatives

July 02, 2025

Production of valuable compounds with potential anti-malarial effects through genetic intervention in enzymatic reactions

An international collaborative research group at the RIKEN CSRS has successfully obtained novel reveromycin (RM) derivatives by engineering enzymes identified from the biosynthetic gene cluster of the microbial metabolite reveromycin A (RM-A), which exhibits diverse biological activities. These new RM derivatives were found to possess structurally stable cores and demonstrated inhibitory effects on the growth of Plasmodium parasites and proliferation of multiple myeloma cells.

RM-A, produced by actinomycetes, exhibits a wide range of biological activities, including selective induction of apoptosis in osteoclasts, suppression of bone metastasis in tumors, anti-periodontal disease effects, and antifungal activity. However, it is known to lose its activity under acidic conditions. In this study, the research group introduced site-specific mutations into the enzyme P450revI involved in RM-A biosynthesis, successfully modifying it to catalyze hydroxylation reactions distinct from those of the wild-type. This approach to manipulating enzymatic reactions opens the door to the creation of further RM derivatives and the development of promising pharmaceutical seeds.

 

Original article

Chemical Science　doi: 10.1039/D5SC01355K

Y. F. Yong, S. Liu, K. Sakai, K. Fujiyama, H. Takagi, Y. Futamura, T. Shimizu, H. Osada, E. B. B. Ong, S. Takahashi,

"Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI".

Contact

Shunji Takahashi
Unit Leader
Natural Product Biosynthesis Research Unit