期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 70, 期 7, 页码 2290-2302出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c06329
关键词
salvianolic acid B; de novo biosynthesis; Saccharomyces cerevisiae; rosmarinic acid biosynthetic pathway
资金
- National Natural Science Foundation of China [81673540, 82173924]
- Natural Science Foundation of Shanghai [16ZR1434100]
Salvianolic acid B (SAB), a water-soluble phenolic acid, has various biological activities and is clinically used for cardio- and cerebrovascular diseases. This study successfully engineered a heterologous rosmarinic acid biosynthetic pathway in yeast, enabling de novo biosynthesis of SAB through cooperation with the native metabolism of the yeast strain.
Salvianolic acid B (SAB), also named lithospermic acid B, belongs to a class of water-soluble phenolic acids, originating from plants such as Salvia miltiorrhiza. SAB exhibits a variety of biological activities and has been clinically used to treat cardio- and cerebrovascular diseases and also has great potential as a health care product and medicine for other disorders. However, its biosynthetic pathway has not been completely elucidated. Here, we report the de novo biosynthesis of SAB in Saccharomyces cerevisiae engineered with the heterologous rosmarinic acid (RA) biosynthetic pathway. The created pathway contains seven genes divided into three modules on separate plasmids, pRS424-FjTAL-Sm4CL2, pRS425-SmTAT-SmHPPR or pRS425-SmTAT-CbHPPR, and pRS426-SmRAS-CbCYP-CbCPR. These three modules were cotransformed into S. cerevisiae, resulting in the recombinant strains YW-44 and YW-45. Incubation of the recombinant strains in a basic medium without supplementing any substrates yielded 34 and 30 mu g/L of SAB. The findings in this study indicate that the created heterologous RA pathway cooperates with the native metabolism of S. cerevisiae to enable the de novo biosynthesis of SAB. This provides a novel insight into a biosynthesis mechanism of SAB and also lays the foundation for the production of SAB using microbial cell factories.
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