中药丹参为唇形科植物丹参（Salvia miltiorrhiza Bge.）的干燥根及根茎，味苦、性微寒，归心肝经，具有活血通络、祛疲止痛、凉血消痈之功效，有“一味丹参，功同四物”之说。丹参酮是丹参主要有效成分之一，在心血管类疾病治疗中发挥重要作用，丹参酮的微生物异源生产能够为含丹参酮中药制剂生产提供大量原材料，降低提取成本，缓解临床用药压力。丹参酮生物合成途径包含多个P450酶，限制了酵母工程菌中丹参酮类化合物产量。本项目聚焦植物P450在微生物中催化效率低引发的工程菌产量低这一国际公认的前沿问题，以中药丹参中三个P450为研究对象，利用定向突变和大肠杆菌-酵母组合菌株构建技术，深入研究并解决丹参中P450在微生物体内催化效率低和工程菌产量低的问题。本项目不仅能在微生物中高效合成多种丹参酮前体化合物，也能为丹参酮ⅡA等活性成分在微生物中全合成奠定基础，为中药活性成分的微生物合成提供思路。

Traditional Chinese medicine Danshen is the dried root and rhizome of Salvia miltiorrhiza Bge with a variety of curative effects. Tanshinones effective components of Danshen, which play an important role in the treatment of cardiovascular diseases. The biosynthesis of tanshinones in microorganisms can provide a large number of raw materials for the production of traditional Chinese medicine, effectively reduce the extraction cost in the production process, and relieve the pressure of clinical use of traditional Chinese medicine. There are many P450 enzymes in tanshinones biosynthesis pathway, which limit the production of tanshinones in the engineering yeast, resulting in a large number of accumulation of P450s substrates and low yield of tanshinones. In this project, three P450s that have been identified in Danshen were improved with directed mutation technology and E.coli-yeast combination strain construction technology, solving the problem of low catalytic efficiency of three P450s in vivo and low yield of tanshinones in microorganism factory. This project can not only obtain a variety of tanshinones in microorganisms effectively, but also lay foundation for the total synthesis of tanshinone IIA in microorganisms cell factory and give a new thought of construction of the traditional Chinese medical plant active components microorganisms cell factory .