丹参素是中药丹参的主要药用成分，其在抗心肌缺血、抗血栓、保肝护肝、抗菌消炎、抗肿瘤等方面疗效显著，具有广泛的临床应用与市场需求。目前，丹参素的主要来源是从丹参中提取或通过化学合成获得，但均存在一定的缺点如产率低、步骤繁琐等问题。生物合成具有周期短、无污染、成本较低等优势，然而天然微生物缺少合成丹参素的代谢途径，有关丹参素的生物合成研究甚少。我们前期通过丹参素毒性测试与菌株代谢途径分析，获得一株耐受性良好且有较强L-Phe合成能力的嗜热地衣芽孢菌。本课题拟以该菌株为对象，首先完成以L-Phe合成前体苯丙酮酸为底物的丹参素非天然合成途径的设计与组装，初步实现丹参素的嗜热合成；其次明确菌株合成丹参素的调控机制，评估解除局部反馈调节和优化整体调控网络对丹参素产量提高的作用；最后以多视角方式建立模块化优化方法，进一步加强丹参素的合成。本研究将为丹参素及苯丙素类化合物的微生物合成提供新策略和理论依据。

Danshensu is the main active component of the traditional Chinese medicine Salvia miltiorrhiza. It has significant curative effect on coronary ischemia, antithrombogenicity, protecting liver, antibacterial and antiinflammatory, and antitumor, which thereby has broad clinical application and huge market demand. Currently, the main source of danshensu is extracted from S. miltiorrhiza or prepared via chemical synthesis, however both of which still exist some disadvantages such as low yield and complicated procedure. Biosynthesis of chemicals has many advantages, whereas natural existed microorganisms lack the pathway for synthesis of danshensu, which leads few study has focused on danshensu biosynthesis. Recently, we selected a thermophilic Bacillus strain which has good tolerance on danshensu and prefers to synthesize more L-phenylalanine. Using this strain, we first aim to design and assemble a non-natural pathyway of danshensu derived from phenylpyruvate the precursor of L-phenylalanine. Then ascertain the regulation mechanism of danshensu biosynthetic pathway and evaluate the influence of removing partial feedback or optimizing the overall regulatory networks on danshensu accumulation. Finally, modular design method will be developed to further improve danshensu production. It is expected that our study will provide a new strategy and theory foundations for microbial synthesis of danshensu as well as phenylpropanoid compounds.