丹酚酸类化合物是中药丹参的主要有效成分之一。以丹酚酸B（SAB）为主要成分制成的现代中药丹参多酚酸盐注射液在治疗心脑血管疾病方面效果显著，临床上应用广泛。目前，丹酚酸B主要从中药丹参中提取。.植物中丹酚酸类化合物由苯丙烷类代谢途径产生，迷迭香酸（RA）是其生物合成途径中第一个结构稳定且具有显著药理活性的化合物。.本项目采用合成生物学思路，以酿酒酵母为底盘细胞，RA为第一目标产物，对植物中RA途径进行设计并重建：以TAL替代PAL和C4H催化的两步反应，借助计算机同源建模与分子对接技术选择候选基因，应用模块策略将RA途径分模块组合优化，将最佳模块构建成基因整合型表达盒，整合入酵母基因组，实现RA途径（Tyr-RA）在酵母中重建；同时，以SAB为第二目标产物，探索并构建由RA到SAB的异源合成途径（RA-SAB）；并进行发酵工艺优化，提高产物得率。.项目成果将为重要药用化合物提供新的生产策略。

Salvianolic acids are the major water-soluble bioactive ingredient in Danshen Radix. Salvianolic acids mainly salvianolic acid B (SAB) have been isolated and prepared as Salvianolate (80% is magnesium Sal B) Injection for clinical usage to cure coronary heart disease and angina. At present, these compounds are derived from danshen roots, in which salvianolic acids are believed to be synthesized through the phenylpropanoid metabolism and rosmarinic acid is the first stable and also a valuable medicinal compound..In this proposal, we want to apply the synthetic biology and use Saccharomyces cerevisiae as host cell to create the mimic RA biosynthesis pathway. To do that, the RA pathway has been re-designed by using TAL to replace PAL and C4H with tyrosine as the initial substrate. Computational-based homology modeling and molecular docking will be employed to predict the appropriate candidate genes. Modular strategy will be adopted to optimize the metabolic flux from the substrate (tyrosine) to the committed product (rosmarinic acid, RA). Besides, the biosynthesis pathway from RA to SAB will be investigated and constructed with the aim to produce SAB in the engineered yeast. Then, the tyrosine to RA pathway will be combined with this RA to SAB construct to create yeast strain harboring the whole pathway from tyrosine to salvianolic acid B. Fermentation optimization will also be performed to achieve high-efficient yields of RA and SAB. .The research in this proposal provides a new way for producing valuable medicinal compounds.