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      HPPR encodes the hydroxyphenylpyruvate reductase required for the biosynthesis of hydrophilic phenolic acids in Salvia miltiorrhiza

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          Salvia miltiorrhiza is a medicinal plant widely used in the treatment of cardiovascular and cerebrovascular diseases. Hydrophilic phenolic acids, including rosmarinic acid (RA) and lithospermic acid B (LAB), are its primary medicinal ingredients. However, the biosynthetic pathway of RA and LAB in S. miltiorrhiza is still poorly understood. In the present study, we accomplished the isolation and characterization of a novel S. miltiorrhiza Hydroxyphenylpyruvate reductase (HPPR) gene, SmHPPR, which plays an important role in the biosynthesis of RA. SmHPPR contained a putative catalytic domain and a NAD(P)H-binding motif. The recombinant SmHPPR enzyme exhibited high HPPR activity, converting 4-hydroxyphenylpyruvic acid (pHPP) to 4-hydroxyphenyllactic acid (pHPL), and exhibited the highest affinity for substrate 4-hydroxyphenylpyruvate. SmHPPR expression could be induced by various treatments, including SA, GA3, MeJA and Ag +, and the changes in SmHPPR activity were correlated well with hydrophilic phenolic acid accumulation. SmHPPR was localized in cytoplasm, most likely close to the cytosolic NADPH-dependent hydroxypyruvate reductase active in photorespiration. In addition, the transgenic S. miltiorrhiza hairy roots overexpressing SmHPPR exhibited up to 10-fold increases in the products of hydrophilic phenolic acid pathway. In conclusion, our findings provide a new insight into the synthesis of active pharmaceutical compounds at molecular level.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 December 2017
          : 15
          : 12
          : 917-927
          1School of Biomedical Sciences, Huaqiao University, Fujian 362000, China
          2Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
          3Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
          Author notes
          *Corresponding authors: TAN He-Xin, ZHANG Lei, and CHEN Wan-Sheng, Tel: 86-21-81871307, E-mail: chenws126@ ; zhanglei@ ; hexintan@

          These authors have no conflict of interest to declare.

          Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: National Natural Science Foundation of China
          Award ID: 81673529
          Award ID: 81325024
          Award ID: 31300159
          Funded by: Shanghai Science and Technology Development Funds
          Award ID: 15391900500
          Award ID: 14QB1402700
          Funded by: National Science and Technology Major Project of China
          Award ID: 2017ZX09101002-003-002
          This work was supported by the National Natural Science Foundation of China (Nos. 81673529, 81325024, and 31300159), Shanghai Science and Technology Development Funds (Nos. 15391900500 and 14QB1402700), and National Science and Technology Major Project of China (No. 2017ZX09101002-003-002).


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