# Recent Advances in Transcription Factor–Mediated Regulation of Salvianolic Acid Biosynthesis in Salvia miltiorrhiza

## TL;DR

This paper reviews how transcription factors control the production of beneficial compounds in Salvia miltiorrhiza, aiming to improve their stable and high-yield production.

## Contribution

The paper synthesizes recent findings on transcriptional regulation of salvianolic acid biosynthesis and proposes strategies for metabolic engineering.

## Key findings

- Transcription factors like SmMYB111 and SmMYC2 activate key genes to boost phenolic acid accumulation.
- Negative regulators such as SmMYB4 and SmMYB39 suppress pathway genes or disrupt activator complexes.
- Future strategies include integrating single-cell omics and genome editing for predictive metabolic engineering.

## Abstract

Salvia miltiorrhiza Bunge is a traditional Chinese medicinal plant whose roots are rich in water-soluble phenolic acids. Rosmarinic acid and salvianolic acid B are representative components that confer antibacterial, antioxidant, and cardio-cerebrovascular protective activities. However, these metabolites often accumulate at low and unstable levels in planta, which limits their efficient development and use. This review summarises recent advances in understanding salvianolic acid biosynthesis and its transcriptional regulation in S. miltiorrhiza. Current evidence supports a coordinated pathway composed of the phenylpropanoid route and a tyrosine-derived branch, which converge to generate rosmarinic acid and subsequently more complex derivatives through oxidative coupling reactions. Key findings on transcription factor families that fine-tune pathway flux by regulating core structural genes are synthesised. Representative positive regulators such as SmMYB111, SmMYC2, and SmTGA2 activate key nodes (e.g., PAL, TAT/HPPR, RAS, and CYP98A14) to promote phenolic acid accumulation. Conversely, negative regulators such as SmMYB4 and SmMYB39 repress pathway genes and/or interfere with activator complexes. Major regulatory features include hormone-inducible signalling, cooperative regulation through transcription factor complexes, and emerging post-transcriptional and post-translational controls. Future directions and challenges are discussed, including overcoming regulatory redundancy and strong spatiotemporal specificity of transcriptional control. Integrating spatial and single-cell omics with functional genomics (e.g., genome editing and rational TF stacking) is highlighted as a promising strategy to enable predictive metabolic engineering for the stable, high-yield production of salvianolic acid-type compounds.