Abstract

Plant diterpenes are of much interest across various industrial sectors including pharmaceuticals, due to their bioactivity and structural complexity. However, the low abundance in the natural host and difficulties in chemical synthesis often limit the development of industrial applications for these compounds. Developing new sustainable production platforms for high-value diterpenoids would improve the supply chains of existing diterpene-derived drugs and provide the confidence needed to exploit the huge potential that this class of compounds has to offer. Multiple “chassis organisms” can be engineered to produce diterpenes, on condition that high levels of the common diterpenoid precursor GGPP are supplied. In this talk, I will present two promising platforms for the production of diterpenes of interest. The first is the notorious Nicotiana benthamiana, in which it is possible to reconstitute a foreign biosynthetic pathway by simple expression of heterologous genes. Over-expression of key genes to increase the endogenous pool of the GGPP precursor proved to be particularly effective, but can yield artefacts if not properly balanced. The second platform involves the use of plant cell cultures, in particular cambial meristematic cells (CMCs) from Taxus spp. The aim here is instead to increase the amount of an endogenous diterpene, paclitaxel, potent anti-cancer drug approved for the treatment of several cancers. I will present the strategies used in each platform to achieve significant amounts of compounds.