发酵法生产利普司他汀的研究进展

Lipstatin is a β-lactone molecule which controls the digestive activity of pancreatic lipases and thus controls the absorption of fat in the small intestine. Lipstatin is supposed to inhibit the catalytic activity of pancreatic lipase by acylation of the serine residue present in the active site. A binding study suggests that one molecule of lipstatin binds with one molecule of lipase. Lipstatin is a natural product produced from Streptomyces toxytricini. The chemical structure is introduced,and the current application situation is reviewed. The progress in production of lipstatin fermentation is presented with a discussion on existing problems. Technology of metabolic engineering used in fermentation is introduced especially.The mechanism of lipstatin biosynthesis in bacteria is not yet clear, however acyl-coenzyme A carboxylase (ACCase) complex is playing key role in lipstatin biosynthesis. Furthermore, prospect for future research is proposed.