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Updated: Jul 29, 2026
Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
1513-DMIa and 1513-DMIb, DNA methyltransferase inhibitors produced by Streptomyces sp. strain No. 1513
1Laboratory of Medicinal Microbiology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Abstract:
Two new methyltransferase inhibitors were isolated from the culture filtrate of Streptomyces sp. strain No. 1513 and named 1513-DMIa and 1513-DMIb. 1513-DMIa and 1513-DMIb were distinguished in certain properties from DMI-1, DMI-2, DMI-3 and DMI-4 previously reported. The molecular weight of 1513-DMIa and 1513-DMIb were estimated to be 576 and 8400 from the results of FAB-MS and gel filtration, respectively. The inhibitory activities of 1513-DMIa and 1513-DMIb were shown to be pH- and temperature-dependent and both inhibited M. EcoRI in an uncompetitive manner with respect to DNA or S-adenosylmethionine (SAM).
Insights
Two novel methyltransferase inhibitors, 1513-DMIa and 1513-DMIb, were discovered from Streptomyces sp. strain No. 1513. These compounds exhibit pH- and temperature-dependent inhibition of M. EcoRI, acting uncompetitively against DNA and S-adenosylmethionine (SAM).
Area of Science:
- Microbiology
- Biochemistry
- Natural Product Chemistry
Background:
- Methyltransferases are crucial enzymes involved in various biological processes.
- Inhibitors of methyltransferases have therapeutic potential.
- Streptomyces species are prolific producers of bioactive secondary metabolites.
Purpose of the Study:
- To isolate and characterize novel methyltransferase inhibitors from Streptomyces sp. strain No. 1513.
- To investigate the properties and inhibitory mechanisms of the newly discovered compounds.
Main Methods:
- Isolation of compounds from culture filtrate using standard chromatographic techniques.
- Determination of molecular weights using Fast Atom Bombardment Mass Spectrometry (FAB-MS) and gel filtration.
- Enzyme inhibition assays to determine the mode of inhibition against M. EcoRI.
Main Results:
- Two new methyltransferase inhibitors, 1513-DMIa and 1513-DMIb, were identified.
- Molecular weights were estimated at 576 (1513-DMIa) and 8400 (1513-DMIb).
- Inhibitory activity was dependent on pH and temperature, with uncompetitive inhibition observed against M. EcoRI concerning DNA and S-adenosylmethionine (SAM).
Conclusions:
- 1513-DMIa and 1513-DMIb represent novel methyltransferase inhibitors with distinct properties.
- The uncompetitive inhibition mechanism provides insights into enzyme-inhibitor interactions.
- These compounds warrant further investigation for their potential applications.
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