Inhibition of DNA methyltransferase by microbial inhibitors and fatty acids.
Streptomyces sp. strain No. 560 produces four kinds of DNA methyltransferase inhibitors in the culture filtrate. One of them, DMI-4 was distinguished from DMI-1, -2 and -3 previously reported with respect to certain properties, DMI-4 is considered to be a triglyceride consisting of the fatty acids anteisopentadecanoic acid (C15:0), isopalmitic acid (C16:0) and isostearic acid (C18:0) from the results of gas chromatography analysis. Since DMI-4 contains three molecules of fatty acid, and the previously reported DMI-1, 8-methylpentadecanoic acid, is analogous to a fatty acid, the inhibitory activity has been examined of various fatty acids and their methyl esters against Eco RI DNA methyltransferase (M. Eco RI). Oleic acid (C18:1) was found to be a potent inhibiton of M. Eco RI. The inhibitory activity of oleic acid was shown to be pH- and temperature-dependent and inhibited M. Eco RI in a noncompetitive manner with respect to DNA or S-adenosylmethionine (SAM). The number of carbon atoms and double bonds in the fatty acid molecule affected the inhibitory activity, but their methyl esters were not inhibitors. Our results suggest that the length of the carbon chain, the number of double bonds and the presence of a carboxyl group and branched methyl group in the fatty acid molecule may play an important role in the inhibition of DNA methyltransferase.[1]References
- Inhibition of DNA methyltransferase by microbial inhibitors and fatty acids. Suzuki, K., Nagao, K., Tokunaga, J., Katayama, N., Uyeda, M. J. Enzym. Inhib. (1996) [Pubmed]
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