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Heterologous overexpression of Nothapodytes foetida strictosidine synthase enhances levels of anti-cancer compound camptothecin in Ophiorrhiza rugosa

Singh, Sudhir, Kamble, Suchita N., Satdive, Ramesh K., Fulzele, Devanand P.
Plant cell, tissue, and organ culture 2020 v.141 no.1 pp. 67-76
Ophiorrhiza, antineoplastic agents, endangered species, gene overexpression, genes, indole alkaloids, mature plants, monoterpenoids, tissues, trees, tryptamine
Nothapodytes foetida, an endangered tree of Indian origin, is a major source of the anti-cancer monoterpenoid indole alkaloid, camptothecin (CPT). Strictosidine synthase (STR) condenses tryptamine and secologanin to form strictosidine, a universal precursor of terpenoid indole alkaloids including CPT. We cloned full-length str cDNA with an open reading frame of 1059 bp from N. foetida (Nfstr) using a homology-based approach. Different tissues of N. foetida from in vitro grown cultures, as well as a mature tree, showed expression of STR, confirming the constitutive nature of the gene. In vitro tissues showed a positive correlation between STR expression and the CPT content, but tissues from wild-type mature plants did not show a similar pattern. Transgenic Ophiorrhiza rugosa plants overexpressing Nfstr showed 1.9-fold higher CPT than non-transformed plants. The results indicated that overexpression of Nfstr in target plants could improve the levels of CPT and may provide an alternative and sustainable source of camptothecin.