Signalling molecules in the modulation of the transcriptome, metabolic flux and triterpene immunoadjuvant saponins biosynthesis in Quillaja brasiliensis Mart. (Quillajaceae)

Abstract

Quillaja brasiliensis is a tree species native to southern Brazil, popularly known as "pão-sabão", which produces bioactive triterpene saponins. Leaf saponins of Q. brasiliensis show pronounced adjuvant activity in experimental veterinary vaccines, comparable to the commercial adjuvant Quil-A®, obtained from Quillaja saponaria bark, a source that is not renewable and is at risk of imminent scarcity. In addition, Q. brasiliensis saponins show significantly lower toxicity compared to Q. saponaria, a very advantageous feature in the use of adjuvant saponins. As in Q. saponaria, among Q. brasiliensis saponins is a specific molecule, QS-21, approved for use in human vaccines against malaria and herpes zoster. Cell cultures of Q. brasiliensis producing saponins are available in the laboratory of the RS proponent, and its use as plant material greatly facilitates transcriptonic and metabolic evaluations. Considering the possibility of Q. brasiliensis use for the sustainable production of saponins with potential commercial use and considering the need for deeper knowledge on the production and accumulation of bioactive saponins, this project aims to characterize metabolic and transcriptional aspects related to production of immunoadjuvant saponins in cell cultures of Quillaja brasiliensis. The characterization will include chemical evaluation, biosynthesis and transcriptional responses in cultures against metabolic elicitors. We expect to better understand the regulation of biosynthesis of triterpenic saponins of high commercial value in cell cultures of Q. brasiliensis and to evaluate their viability as an alternative and / or complementary source of these natural products and, in the long term, to subsidize the production biotechnology in heterologous systems. (AU)