佛司可林生物合成研究进展

Recent advances in biosynthesis of forskolin

佛司可林(forskolin)是一种结构复杂的半日花烷型植物二萜,基于其作为环磷酸腺苷(cAMP)环化酶激活剂的活性,被用于多种疾病的治疗。天然的佛司可林目前仅存在于濒危植物毛喉鞘蕊花根的木栓层中,因提取和化学合成过程复杂,其产量和纯度无法满足商业需求。随着近年合成生物学的快速发展及许多二萜生物合成途径的解析,为佛司可林的绿色生产提供了新途径。该研究对佛司可林的结构与活性、生物合成途径及异源生物合成进行了综述,并对异源生物合成佛司可林存在的问题及解决方案进行了探讨与归纳,为构建高产佛司可林工程细胞提供参考。

Forskolin is a complex labdane plant diterpenoid,which has been used in the treatment of a variety of diseases based on its activity as an activator of adenosine monophosphate(cAMP)cyclase.Natural forskolin exists only in the cork layer of the root of Coleus forskohlii.Due to the complexity of the extraction and chemical synthesis processes,the yield and purity of forskolin cannot meet commercial requirements.In recent years,with the rapid development of synthetic biology and the analysis and interpretation of many diterpene biosynthetic pathways,a new approach has been provided for the green production of forskolin.In this paper,the structure,activity,biosynthetic pathway and the heterologous biosynthesis of forskolin were reviewed.The problems and solutions in the heterologous biosynthesis of forskolin were also discussed and summarized,which will provide references for the construction of high-yielding forskolin engineering strains.