UCF116, New Inhibitors of Farnesyltransferase Produced by Streptomyces

Farnesyltransferase (FTase) catalyses the farnesylation of Ras p21 protein on a cysteine residue of a carboxyl-terminal CAAX motif. This post-translational modification is necessary for their association with plasma membranes and oncogenic activity. Therefore, inhibition of Ras farnesyltransferase presents a potential therapeutic target for novel anticancer agents. Recently, several natural product inhibitors of FTase have been reported including manumycin, andrastin D, clavaric acid, and kampanol B. Our microbial product screening efforts have now led to the isolation of new inhibitors of FTase, UCF116-A (1), -B (2) and -C (3), produced by Streptomyces sp. In this paper, fermentation, isolation and biochemical properties of UCF116 are described.