## 7 Biosynthetic Pathways of Transcription Factors, Signaling Molecules and Secondary Metabolites  
The significance of metabolic engineering resides in the fact that it will unleash the capabilities of improving the production of beneficial secondary metabolites or focusing on the improvement of the plant's resistance to abiotic stresses such as salt and drought stresses. There is a strong correlation between stress-induced genes and secondary metabolite production. However, some secondary metabolite-encoding genes are considered stress-induced genes since they carry out protective roles and are induced during exposure to stress. Primary signals in most environmental stresses involve reactive oxygen species (ROS); hormones such as ethylene, JA and abscisic acid (ABA); transcription factors (TFs); and other signaling molecules. TFs, which are DNA-binding proteins, have an indispensable job in the regulation of secondary metabolite production in plants because they control the expression of many genes that play multiple roles in the metabolic pathway. However, it was demonstrated by studies on many plants that JA contributes to the transcriptional activation of many TFs that are used to boost the expression of specific biosynthetic genes for secondary metabolites. For instance, _MYC2_, aHLH-type transcription factor, has been identified as the regulatory center of the JA-signaling pathway, thereby affecting secondary metabolite accumulation in various plant species including _Artemisia annua_, _Nicotiana tabucum_ and _Catharanthus roseus_[6, 95]. Additionally, the _AtMYB12_ gene, which encodes for a stress-inducible transcription factor, is responsible for the modulation of the expression of genes involved in the phenylpropanol pathway which would result ultimately in enhanced production of secondary metabolites. A study conducted by [PERSON] [96] suggested that overexpression of the _A. thaliana_ gene that encodes for a calcium-dependent protein kinase (_AtCPKI_) in the medicinal plant _R. cordifolia_ caused a substantial increase in the anthraquinone content production in the transgenic plant. The calcium-dependent protein kinases are strongly induced when plants are adapting to drought and salinity stresses, as reported above. Exogenous application of jasmonates, specifically MeJA, should enhance production of the secondary metabolite flavonoid (anthocyanin) in the model plant Arabidopsis thaliana  
Figure 3: (**A**) The artemisinin biosynthetic pathway. (**B**) Jasmonic acid elicitation of artemisinin in the plant _Artemisia annua_. JA content is increased when the plant Artemisia annua is exposed to salinity or drought stresses. The increased JA level leads to the activation of two AP2/ERF transcription factors (AaERF1 and AaERF2) that bind to the CBF2 and RAA _cis_-acting elements that are found on the promoter regions of the _ADS_ and _CYP_ genes that are major components of the artemisinin biosynthesis pathway. and other plants. MeJA participates in the regulation of the monoterpenoid indole alkaloid (MIA) biosynthetic pathway in the well-studied medicinal plant _C. roseus_ by coordinately inducing the expression of biosynthetic-related genes (Figure 2). Promoter analysis study showed that specific AP2/EREBP transcription factors known as octadecanoid-derivative responsive Catharanthus AP2-domain protein 1 (_ORCA1_) and _ORCA2_ have a strong relation to the expression of important MIA biosynthetic genes [40; 97]. _ORCA2_ showed strong relation to the MeJA-responsive MIA biosynthesis genes, such as the strictosidine synthase (_STR_) gene (Figure 2). Further research has identified _CrMYC2_, another transcription factor belonging to the bHLH family of transcription factors, as a major activator of MeJ-responsive _ORCA3_ gene expression. An experiment conducted by [PERSON] [95] involving knockdown mutant of the _CrMYC2_ expression level by RNAi technique showed results indicating that expression levels of _ORCA3_ and _ORCA2_ were reduced significantly.