雷帕链霉菌次级代谢产物及其生物合成的研究进展

摘要：雷帕链霉菌(Streptomyces rapamycinicus)是一种重要的工业菌株，主要用于生产新型大环内酯类抗生素——雷帕霉素。该抗生素具有抗真菌、抗肿瘤、免疫抑制和抗衰老等众多生物活性，临床上主要用作器官移植的免疫抑制剂以及抗肿瘤药物。全基因组测序表明，雷帕链霉菌野生型菌株NRRL5491基因组全长12.7Mb，编码多达48个次级代谢产物生物合成基因簇(共长达3Mb)，证明其具备强大的次级代谢潜力。除雷帕霉素以外，至今已有多种活性天然产物被鉴定，包括放线菌酸、尼日利亚菌素、洋橄榄叶素、安莎类抗生素和六烯类抗生素等，相关合成基因簇及其生物合成途径已被解析。本文将就雷帕链霉菌中各种次级代谢产物的生物学功能、生物合成基因簇及其生物合成过程等研究进展进行总结梳理，并就如何更好挖掘雷帕链霉菌中的活性天然产物进行简单展望与讨论。

Research progress on secondary metabolites and their biosynthesis in Streptomyces rapamycinicus

Abstract Streptomyces rapamycinicus is an important industrial strain, which is mainly used to produce a newtype of macrolide antibiotic-rapamycin. The antibiotic has many biological activities such as anti-fungal, anti-tumor,immunosuppression, and anti-aging, and is mainly used clinically for immunosuppression of organ transplantationand anti-tumor. Whole-genome sequencing shows that the full-length genome of S. rapamycinicus NRRL5491 is12.7Mb, which encodes as many as 48 secondary metabolite biosynthetic gene clusters (a total of 3Mb), proving thatit has strong secondary metabolic potential. In addition to rapamycin, a variety of active natural products have beenidentified so far, including actinoplanic acids, elaiophylin, nigericin, hexaenes, and hygrocins, and related biosyntheticgene clusters and biosynthesis pathways have been resolved. This article summarizes the research progress of thebiological functions, biosynthetic gene clusters and biosynthesis processes of various secondary metabolites in S.rapamycinicus. Furthermore, we also give a brief outlook and discussion on how to better explore the active naturalproducts in this important industrial bacterium.