创新霉素生物合成研究进展

Research progress on the biosynthesis of chuangxinmycin

创新霉素是中国科学家20世纪60年代发现的具有全新骨架结构的抗生素,由济南游动放线菌产生,具有良好的抗菌活性和新颖的作用靶点,但创新霉素的生物合成基因簇在其发现50多年后才得到解析。本文介绍了创新霉素研究的历史沿革,着重介绍了其生物合成机制的最新研究进展,从生物合成基因簇、生物合成途径、新颖的去泛素化酶样的硫转移酶催化的硫掺入机制、罕见的细胞色素P450酶催化的C-S键形成机制等角度进行阐述,这些研究进展为利用组合生物合成和合成生物学技术进行新药研发和高产优产奠定了理论基础。

Chuangxinmycin is an antibiotic isolated from Actinoplanes tsinanensis in the 1960s with a novel indole-dihydrothiopyran heterocyclic skeleton.It showed good antibacterial activity and unique antibacterial mechanism.However,its biosynthetic gene cluster has remained obscure for over 50 years.The historical evolution of chuangxinmycin research was introduced,and the latest advances in the understanding of its biosynthetic mechanism were reviewed in detail from the perspectives of biosynthetic gene cluster,biosynthetic pathway,the novel mechanism for sulfur incorporation catalyzed by a deubiquitinase-like sulfurtransferase and the rare C-S bond formation mechanism catalyzed by cytochrome P450 enzyme.The elucidation of the biosynthetic mechanism of chuangxinmycin provides the basis for applying combinatorial biosynthesis and synthetic biology technology in generating diverse structures for new drug discovery and development.