化工进展 ›› 2021, Vol. 40 ›› Issue (4): 2251-2257.DOI: 10.16085/j.issn.1000-6613.2020-1653

• 生物与医药化工 • 上一篇    下一篇

发酵法生产利普司他汀的研究进展

李玲1(), 于泳1, 胡永红2()   

  1. 1.东南大学成贤学院制药与化学工程学院,江苏 南京 210088
    2.南京工业大学生物与制药工程学院,江苏 南京 211816
  • 收稿日期:2020-08-18 出版日期:2021-04-05 发布日期:2021-04-14
  • 通讯作者: 胡永红
  • 作者简介:李玲(1986—),女,讲师,研究方向为发酵工程制药。E-mail:liling040911@163.com
  • 基金资助:
    江苏省科技计划(BE2018396);东南大学成贤学院青年教师科研发展基金(z0033)

Research progress in production of lipstatinfermentation

LI Ling1(), YU Yong1, HU Yonghong2()   

  1. 1.Department of Pharmaceutical and Chemical Engineering, Southeast University Chengxian College, Nanjing 210088, Jiangsu, China
    2.College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu, China
  • Received:2020-08-18 Online:2021-04-05 Published:2021-04-14
  • Contact: HU Yonghong

摘要:

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。

关键词: 利普司他汀, 发酵, 代谢工程, 毒三素链霉菌

Abstract:

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.

Key words: lipstatin, fermentation, metabolic engineering, Streptomyces toxytricini

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