喷司他丁的合成及其生物合成机制研究进展  

Advances in the biosynthesis of pentostatin

作　　者：宋泽祺 刘虎虎[1,2] 段希宇 杨辉 王翀[1,2] 卢向阳 田云[1,2] Zeqi Song;Huhu Liu;Xiyu Duan;Hui Yang;Chong Wang;Xiangyang Lu;Yun Tian(College of Bioscience and Biotechnology,Hunan Agricultural University,Changsha 410128,Hunan,China;Key Laboratory for Agricultural Biochemistry and Biotransformation of Hunan Provincial University,Changsha 410128,Hunan,China)

机构地区：[1]湖南农业大学生物科学技术学院,湖南长沙410128 [2]农业生物化学与生物转化湖南省高校重点实验室,湖南长沙410128

出　　处：《生物工程学报》2021年第12期4158-4168,共11页Chinese Journal of Biotechnology

基　　金：国家自然科学基金(No.21808052);中国博士后科学基金(No.2019TQ0088);湖南农业大学“双一流”建设项目(No.SYL201802002);长沙市杰出创新青年培养计划(No.kq2009019)资助。

摘　　要：喷司他丁是一种核苷类抗生素,对腺苷脱氨酶有极强的抑制效果,在临床治疗恶性肿瘤方面具有广泛应用。但其生产成本高、市售价格昂贵,难以满足需求。近10年来,关于生物合成喷司他丁的研究主要集中在菌种选育、优化培养基组分与发酵工艺等方面。目前,尽管喷司他丁的生物合成机制得到了阐明,但生物合成喷司他丁方面的综述尚无。对此,文中综述了喷司他丁的生物合成进展,为其进一步研究提供参考。首先,简介了喷司他丁的合成方法及其生产现状;其次,总结了喷司他丁在不同微生物中的生物合成机制;最后,探讨了生物合成喷司他丁所面临的问题,并提出调控微生物合成喷司他丁的策略,以期为喷司他丁的规模化生产提供指导。Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase,and is widely used in the clinical treatment of malignant tumors.However,the high cost hampers its application.In the past 10 years,the biosynthesis of pentostatin were focused on strain breeding,optimization of medium composition and fermentation process.To date,there are no reviews summarizing the elucidated biosynthetic mechanism of pentostatin.This review starts by introducing the various chemical route for production of pentostatin,followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.

关 键 词：喷司他丁 核苷类抗生素 生物合成 微生物发酵 系统代谢工程 

分 类 号：TQ465[化学工程—制药化工]