SmERF6 promotes the expression of terpenoid pathway in Salvia officinalis and improves the production of high-value abietane diterpenes, carnosol and carnosic acid.

This article focuses on enhancing the biosynthesis of pharmaceutically important diterpenes, carnosol (CO) and carnosic acid (CA), in Salvia officinalis (garden sage) by heterologous overexpression of the transcription factor SmERF6 (Salvia miltiorrhiza Ethylene Responsive Factor 6). SmERF6, previously shown to regulate tanshinone biosynthesis in S. miltiorrhiza by binding to promoters of key diterpene biosynthetic genes (CPS and KSL), was transiently and stably expressed in S. officinalis, resulting in significant upregulation of CO and CA biosynthetic genes and a 2- to 5-fold increase in metabolite accumulation. The study also demonstrated tissue-specific and developmental regulation of CO biosynthesis in garden sage, induction of the pathway by methyl jasmonate, and developed an Agrobacterium-mediated in planta transformation method for stable transgenic lines. These findings provide the first evidence that pathway-specific transcription factor engineering can effectively improve the in planta content of high-value diterpenes in S. officinalis, offering potential for commercial-scale production of these medicinal compounds.