capítulos de libros
Biotechnological approaches for the improvement in the production of tropane alkaloids: implications and medicinal applications
Alkaloids: Biosynthesis, Biological Roles and Health Benefits
Nova Science Publishers
Año: 2015; p. 131 - 154
Hyoscyamine, anisodamine (6b-hydroxyhyoscyamine) and scopolamine are the most important tropane alkaloids from a therapeutical point of view. These alkaloids are well known anticholinergic agents and were historically used in medicine.  Scopolamine is the more valuable alkaloid, having a 10 times higher commercial demand than that of hyoscyamine. Further therapeutical properties were described for anisodamine that includes the treatment of microvascular diseases, glomerulonephritis, rheumatoid arthritis, gastrointestinal colic, eclampsia as well as the control of toxic shock, septic shock, and organophosphorus poisoning. Moreover, anisodamine is not as toxic as atropine, having lesser negative effects on the Central Nervous System than scopolamine.  Since chemical synthesis of tropane alkaloids is difficult and expensive, these compounds are still extracted from plants belonging to several species of Solanaceae family including, Hyoscyamuns niger L., Anisodus tanguticus, Scopolia tangutica Maxim, Atropa belladonna, and several Datura species.  Obtaining these compounds by in vitro culture techniques is an interesting alternative since it guarantees a stable and uniform year round supply, independent of weather and soil conditions. Undifferentiated cultures fail to produce tropane alkaloids or produce them at a low level. In order to increase the production of these secondary metabolites several strategies have been assayed.  Some of them were the application of differentiated cultures such as hairy roots obtained by the transformation with Agrobacterium rhizogenes, media design, elicitation and the genetic engineering approach. However, the results obtained to date were not applicable for an industrial scale production.  In addition to the advantages mentioned before, plant organ cultures such as hairy roots were useful models in the study of secondary metabolic pathways. From these cultures it was possible the isolation of different key enzymes and its characterization.  Furthermore, the expression of plant genes in microorganisms represents an interesting strategy for the production of plant enzymes and/or the products derived from its activity. The production of the more valuable alkaloids by biocatalytic processes appears to be a promising strategy.  In this chapter we discuss the implications and the results of the different approaches for the improvement of tropane alkaloids production in order to replace the isolation from the natural source.