发酵法生产利普司他汀的研究进展

Research progress in production of lipstatin fermentation

利普司他汀(lipstatin)是一种β-内酯分子,能选择性抑制胰脂肪酶的活性,从而减少小肠脂肪的吸收。分析表明,一个利普司他汀分子与一个脂肪酶分子结合,通过活性部位丝氨酸残基的酰化来抑制胰脂肪酶的催化活性。利普司他汀由毒三链霉菌(Streptomyces toxytricini,简称S.toxytricini)生产的一种天然产物。本文综述了利普司他汀的结构特点,分析了利普司他汀市场应用现状,着重论述了发酵法生产利普司他汀的研究进展;提出生物合成利普司他汀的机制尚不清楚,但酰基辅酶A羧化酶(ACCase)复合物在利普司他汀生物合成中起着关键作用。最后,指出当前存在的问题并对代谢工程在利普司他汀产生菌发酵中的应用进行概述,对今后的研究趋势进行了展望。

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.