Signal transduction engineering is important to enhance secondary metabolite production. In this work, the effect of several heavy salts including NH4VO3, NaVO3, VOSO4, NiSO4, CuSO4 and MnSO4 on the ginsenoside biosynthesis in suspension cultures of Panax ginseng was investigated and vanadate was demonstrated most efficient. The optimal concentration and time of vanadate addition was 50 mu M and on day 4, respectively. The maximal content of ginsenosides (Rg1 + Re + Rb1 + Rc + Rd) was 564.3 +/- 12.4 mu g/100 mg DW (day 14) in vanadate treated cultures, while that was only 136.2 +/- 13.3 mu g/100 mg DW (day 17) in the control. The ginsenoside content enhancement coincided with increased activities of UDPG-ginsenoside Rd glucosyltransferase and protopanaxadiol 6-hydroxylase. To further understand the mechanism of vanadate elicitation, jasmonic acid (JA) content and transcriptional levels of genes encoding enzymes related to the triterpene biosynthesis were examined. Upon vanadate treatment, the induction of endogenous JA biosynthesis and up-regulation of transcription levels of sqs, se and ds genes were observed. Interestingly, addition of ibuprofen, an inhibitor of JA biosynthesis, reversed all those effects. The results indicate that vanadate may induce the ginsenoside biosynthesis by inducing the signal molecule JA, and vanadate addition was an effective strategy for increasing ginsenoside production. (C) 2013 Elsevier Ltd. All rights reserved.