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Screening of microbial secondary metabolites inhibiting cholesterol biosynthesis with the use of hepatoblastoma G2]
Authors:A S Trenin  L P Terekhova  I V Tolstykh  V A Zenkova  G B Fedorova  G S Katrukha
Affiliation:G. F. Gause Research Institute of New Antibiotics, Russian Academy of Medical Sciences, Moscow.
Abstract:The culture of hepatoblastoma G2 (Hep G2) cells is proposed as an effective model for screening of microbial metabolites--inhibitors of sterol biosynthesis. This model can be applied at early stages of screening procedures and is quite effective for testing of crude extracts of producers' culture broth. The test is based on measurement inhibition of the radiolabelled precursors incorporation in cholesterol and separate fractions of lipids by microbial metabolites in Hep G2 cells. That allows not only to reveal inhibitors of cholesterol biosynthesis, but also to evaluate mechanism of action, including ability to inhibit the synthesis of cholesterol ethers. The cholesterol biosynthesis inhibition was tested at 150 microbial cultures (actinomycetes and imperfect fungi), isolated from soil. The ability to inhibit 14C-acetate incorporation into cholesterol was found in 15-20% of microbial cultures possessing antifungal activity of extracts (culture broth and mycelium).
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