Progress in synthetic biology of scutellarin and scutellarin

On December 3, the international academic journal metabolic engineering published on-line a paper by Wang Yong, research group, center of excellence and innovation in Molecular Plant Science / Institute of plant physiology and ecology, Chinese Academy of Sciences, entitled production of plant specific flavors baicalein and scutellarein an engineered E coli from available phenylalanine and tyrosine Baicalein is a kind of flavonoid compound It is the main active component extracted from the dried root of Scutellaria baicalensis Georgi, a perennial herb in Labiatae It is also one of the material bases for the pharmacological action of Scutellaria baicalensis Georgi In recent years, a large number of in vivo and in vitro experiments have proved that baicalin has a wide range of biological and pharmacological activities, such as anti-oxidation, anti-inflammatory, anti apoptosis and improving learning and memory ability It has a wide range of action spectrum, multiple action sites, and complex mechanism of action, and is expected to become a safe, cheap and broad-spectrum effective anti-tumor Drugs and potential ideal drugs for the treatment of Alzheimer's disease Scutellarin is mainly found in Erigeron karvinskianus, a Compositae plant, which has the functions of anti-inflammatory and analgesic, promoting blood circulation and removing blood stasis, removing wind and dampness These two compounds are expected to be developed into new drugs for the benefit of mankind, but their natural content in plants is less How to obtain high-purity compounds efficiently and cheaply is an urgent problem to be solved It is an effective way to solve the above problems by using synthetic biology technology to achieve high-efficiency directional synthesis and large-scale preparation Although the two compounds come from different plants, their structures are similar The difference lies in whether there is hydroxyl substitution at the 4 'position of the B-ring of the flavonoid nucleus In view of this, the researchers constructed a kind of E.coli which can synthesize scutellarin or scutellarin with 11 genes from 7 different species They only need to provide two different precursors, phenylalanine or tyrosine, to obtain these two important flavonoids Firstly, the genes of 4CL and fnsi from parsley, pal from rhodotorulouides, CHS from Petunia hybrida and chi from Medicago sativa were used to construct the synthesis module of salicin / apigenin, the important intermediate of flavonoids Furthermore, we cloned f6h and atcpr genes from Scutellaria baicalensis Georgi and Arabidopsis thaliana, and introduced different solubilizing tags to optimize their expression, thus realizing the heterologous synthesis of scutellarin and scutellarin On this basis, the researchers further modified the supply of malonyl COA, an important precursor, by overexpression of malonyl COA synthesis gene ACS and fatty acid synthesis gene fabf, and introduced malonyl COA synthetase gene matb and malonate from Rhizobium trifolii The carrier protein) gene, matc, finally achieved the output of scutellarin 23.6 mg / L and scutellarin 106.5 mg / L in shake flask level in E.coli This study provides an alternative to the large-scale development and manufacture of scutellarin and scutellarin independent of plant extraction, and also provides a reference strategy for the synthesis and biological manufacture of other flavonoids The research work was completed by Li Jianhua, assistant researcher of Wang Yong research group, Tian Chenfei, Xia Yuhui, and other graduate students The research work was supported by NSFC, Center for excellence and innovation of molecular plant science of Chinese Academy of Sciences, and strategic leader B of Chinese Academy of Sciences.