The Expression Profiles of the Salvia miltiorrhiza 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase 4 Gene and Its Influence on the Biosynthesis of Tanshinones

Małgorzata Majewska; Piotr Szymczyk; Jan Gomulski; Agnieszka Jeleń; Renata Grąbkowska; Ewa Balcerczak; Łukasz Kuźma

doi:10.3390/molecules27144354

The Expression Profiles of the Salvia miltiorrhiza 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase 4 Gene and Its Influence on the Biosynthesis of Tanshinones

Molecules. 2022 Jul 7;27(14):4354. doi: 10.3390/molecules27144354.

Authors

Małgorzata Majewska¹, Piotr Szymczyk¹, Jan Gomulski¹, Agnieszka Jeleń², Renata Grąbkowska¹, Ewa Balcerczak², Łukasz Kuźma¹

Affiliations

¹ Department of Biology and Pharmaceutical Botany, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.
² Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.

Abstract

Salvia miltiorrhiza is a medicinal plant that synthesises biologically-active tanshinones with numerous therapeutic properties. An important rate-limiting enzyme in the biosynthesis of their precursors is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). This study presents the organ-specific expression profile of the S. miltiorrhiza HMGR4 gene and its sensitivity to potential regulators, viz. gibberellic acid (GA₃), indole-3-acetic acid (IAA) and salicylic acid (SA). In addition, it demonstrates the importance of the HMGR4 gene, the hormone used, the plant organ, and the culture environment for the biosynthesis of tanshinones. HMGR4 overexpression was found to significantly boost the accumulation of dihydrotanshinone I (DHTI), cryptotanshinone (CT), tanshinone I (TI) and tanshinone IIA (TIIA) in roots by 0.44 to 5.39 mg/g dry weight (DW), as well as TIIA in stems and leaves. S. miltiorrhiza roots cultivated in soil demonstrated higher concentrations of the examined metabolites than those grown in vitro. GA₃ caused a considerable increase in the quantity of CT (by 794.2 µg/g DW) and TIIA (by 88.1 µg/g DW) in roots. In turn, IAA significantly inhibited the biosynthesis of the studied tanshinones in root material.

Keywords: GA3; HMGR4; IAA; SA; Salvia miltiorrhiza; expression; overexpression; tanshinone.

MeSH terms

Abietanes
Acyl Coenzyme A
Coenzyme A
Furans
Oxidoreductases / metabolism
Phenanthrenes
Plant Roots / genetics
Plant Roots / metabolism
Quinones
Salvia miltiorrhiza* / metabolism
Salvia*

Substances

Abietanes
Acyl Coenzyme A
Furans
Phenanthrenes
Quinones
tanshinone
3-hydroxy-3-methylglutaryl-coenzyme A
dihydrotanshinone I
Oxidoreductases
Coenzyme A

Grants and funding

This research was funded by by the Medical University of Lodz (grant nos. 502-03/3-012-02/502-34-103, 503/3-012-01/503-31-001-19-00, 503/3-015-02/503-31-001-19-00).