Scopolamine metabolic engineering

Another metabolically engineered plant species was Scopolia parviflora. The transgenic lines that overexpressed tobacco pmt mRNA produced high PMT protein levels, and displayed enhanced hyoscyamine and scopolamine amounts [133]. 

Palazon, J., Navarro-Ocana, A., Hemandez-Vazquez, L., and Miijalili, M. H. (2008) Application of metabolic engineering to the production of scopolamine. Molecules. 13, 1722-1742. 

The current status of knowledge of the biosynthesis of the tropane alkaloids is almost paradoxical our understanding of the mechanisms by which plants assemble the tropane nucleus (1) still leaves much to be desired whilst some of the late events in the formation of one particular tropane alkaloid, scopolamine (2), are understood in great detail. Applications of this knowledge in the sense of metabolic engineering of medicinal plants have even been described [5]. 

Fig. 8.10 Single-step metabolic engineering in Atropa belladonna for scopolamine production...

Nevertheless, genetic engineering of a key enzyme in a chosen pathway does not always result in the enhancement of the end product thus, overexpression of pmt gene carried out in A. belladonna resulted in a 5-fold increased in pmt transcript level but an unchanged tropane alkaloid profile (hyoscyamine and scopolamine), as well as the tropane alkaloids biosynthetic precursors tropine, pseudotropine and tropinone which were not affected [134-135], Similarly, the overexpression of tobacco pmt gene in Dubosia hybrid hairy root cultures produced amounts of tropane alkaloid similar to control roots [131, 136]. All these results seem to indicate the presence of different points of control in the tropane alkaloid metabolic pathway. 

It has been demonstrated that H6H catalyses the formation of scopolamine from hyoscyamine. Besides, the encoding h6h gene has been identified and sequenced. Thus, the genetic engineering of this metabolic step offers great interest for scopolamine enhancement in... 

---