Characteristics of the squalene synthase inhibitors produced by a Streptomyces species isolated from soils.
Microorganisms producing squalene synthase inhibitors were screened from soils. A high producer was selected and identified as a Streptomyces species. Two active inhibitors were obtained from culture broths via a series of purification processes involving solvent extraction, WK-10 cation-exchange column chromatography, HP-20 adsorption column chromatography, silica-gel column chromatography, preparative HPLC, and crystallization. The inhibitors were confirmed as macrolactins A and F with molecular weights of 402 by UV-absorption spectrometry, fast atom bombardment mass spectometry, and 13C- and 1H-NMR analyses. Kinetic results for macrolactins A and F showed that they appear to be noncompetitive inhibitors of rat liver squalene synthase with IC50 values of 1.66 and 1.53 micromol/L, respectively. Since mammalian squalene synthase was used, these inhibitors have significant potential as therapeutic agents for hyperlipemia and suppression of cholesterol biosynthesis.
Choi
Sung-Won
SW
Green Biotech Co. Ltd., Paju-city, Gyeonggi-do, South Korea.
Bai
Dong-Hoon
DH
Yu
Ju-Hyun
JH
Shin
Chul Soo
CS
D000818:Animals; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D051381:Rats; D012988:Soil Microbiology; D013302:Streptomyces / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*
D018942:Macrolides; C453562:macrolactin A; D013186:Farnesyl-Diphosphate Farnesyltransferase