DMI-1, a new DNA methyltransferase inhibitor produced by Streptomyces sp. strain No. 560.
A new inhibitor of DNA methyltransferase named DMI-1 has been discovered in the culture filtrate of Streptomyces sp. strain No. 560. DMI-1 was purified by extraction with ethyl acetate followed by Diaion HP-20SS and silica gel column chromatography. The structure of DMI-1 was determined to be 8-methylpentadecanoic acid (C16H32O2). DMI-1 is a novel inhibitor of methyltransferase isolated from microorganisms and is structurally different from sinefungin and A9145C which are structural analogs of S-adenosylmethionine (methyl donor). DMI-1 was a strong inhibitor of N6-methyladenine-DNA methyltransferase (M. Eco RI, EC 2.1.1.72) in a noncompetitive manner and its inhibition depended on the pH and temperature in the assay media.
Suzuki
K
K
Laboratory of Medicinal Microbiology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Nagao
K
K
Tokunaga
J
J
Hirosawa
M
M
Tsubone
H
H
Uyeda
M
M
D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D003851:Deoxyribonucleases / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D012260:Ribonucleases / Q000187:drug effects; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000037:antagonists & inhibitors; D013302:Streptomyces / Q000737:chemistry*; D013696:Temperature
C098700:8-methylpentadecanoic acid; D005227:Fatty Acids; D015254:DNA Modification Methylases; C020098:DNA modification methylase EcoRI; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D003851:Deoxyribonucleases; D012260:Ribonucleases