Preliminary Modeling Screening For Fatty Acid Synthase FabB/F Inhibitor

Fatty acid synthase (FAS) is a key enzyme serve as catalyze the synthesis of endogenous long-chain fatty acid. Because of the diffenents between mammalian and bacterium in the synthetic route of fatty acid, it is become a promising target for screening the FAS inhibitor. At present, FAS inhibitor was confirmed have a notable effect for bacterium restrain, weight reduction and tumor treatment, and also high-efficient, low toxicity, perfermance stabilize, especially the development of novel FAS inhibitor combine with multi-targets has been research focus. Now, there seldom FAS inhibitor were reported, however, the red-hot research was go in for from natural products screening for FAS inhibitor, or improve the stucture of medicine applied in weight reduction, bacterium restraint and fucntional enzymes. In addition, some methods of computer simulation also make advancement in find and design of FAS inhibitors.Here, Burkholderia cepacia (BC) was been a gaol strain in this study, mutagenize was performed, and we obtained a mutant with oleic acid auxotrophic and resistance of Cerulenin (a efficient FAS inhibitor). It was identified as FabB/F experssion deficient. So, in this study we proposal that use the double targets FabB/F to establish a screening model, and the two plates method was applied to targeting to fatty acid synthase inhibitor from the plants extractive and microbial metabolin. Meanwhile, Cerulenin that well-known effective FASI were used to made a standard for screening FASI, nine compounds were used to detect the feasibility of this screening model, which known as treatment of obesity and cancer or antibacterial. We obtained three compounds which have strong activity, they are Rhein, Emodin, Quercetin. And the chemical structure diff analysis shown that have some similar between Rhein, Emodin and Cerulenin in part Carbon bone structure. So, here we can determinate its maybe FASI which targeting to FabB/F.The experiments result shown that the screening model has a good performance for selective FASI, so, it can be make use of selection and identification for target compounds.