the c4h, tat, hppr and hppd genes prompted engineering of rosmarinic acid biosynthetic pathway in salvia miltiorrhiza hairy root cultures答,c4h hppr和hppd rosmarinic酸生物合成途径的基因促使工程丹参毛状根的文化.pdfVIP

The c4h, tat, hppr and hppd Genes Prompted Engineering of Rosmarinic Acid Biosynthetic Pathway in Salvia miltiorrhiza Hairy Root Cultures 1,5. 2,4. 1 4 1 1 Ying Xiao , Lei Zhang , Shouhong Gao , Saengking Saechao , Peng Di , Junfeng Chen , Wansheng Chen1,3* 1 Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China, 2 Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China, 3 Modern Research Center for Traditional Chinese Medicine, Second Military Medical University, Shanghai, People’s Republic of China, 4 Department of Plant Sciences, University of California Davis, Davis, California, United States of America, 5 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Abstract Rational engineering to produce biologically active plant compounds has been greatly impeded by our poor understanding of the regulatory and metabolic pathways underlying the biosynthesis of these compounds. Here we capitalized on our previously described gene-to-metabolite network in order to engineer rosmarinic acid (RA) biosynthesis pathway for the production of beneficial RA and lithospermic acid B (LAB) in Salvia miltiorrhiza hairy root cultures. Results showed their production was greatly elevated by (1) overexpression of single gene, including cinnamic acid 4-hydroxylase (c4h), tyrosine aminotransferase (tat), and 4-hydroxyphenylpyruvate reductase (hppr), (2) overexpression of both tat and hppr, and (3) suppression of 4-hydroxyphenylpyruvate dioxygenase (hppd). Co-expression of tat/hppr produced the most abundant RA (906 mg/liter) and LAB (