Plants are capable of producing a vast array of biomolecules that can be exploited for biomedicine. For example, 73% of anticancer drugs have been made from natural products, many from plants, since the 1940s.

Plant products are characteristically chemically complex, their synthesis is routinely difficult, and often not commercially viable. The result is that many of these molecules must be obtained directly from the source plant which raises a series of other significant problems including slow growth, inability to grow at scale, limited populations and variable concentrations of target chemicals. An alternative production system is therefore often required.

Paclitaxel is a World Health Organisation (WHO) essential medicine, for which demand outstrips supply. Eight sixty-year-old trees are required to produce enough paclitaxel to treat one cancer patient.

The global paclitaxel API market is currently valued at $107.3M.

Challenge

Complete chemical routes to produce paclitaxel are not economically viable and semi-synthetic routes are expensive and produce toxic by-products. The project partners wanted to employ new strategies in a cultured plant cell biomanufacturing platform to produce paclitaxel.

Solution

Innovation funding from IBioIC enabled the project partners to test a new strategy to elucidate the natural production mechanisms used by Taxus brevifolia, also known as the Pacific Yew, and engineer them in faster growing plant cells.

Gary Loake’s team produced DNA constructs for the stable expression of the enzymes and regulators required to produce paclitaxel. These were inserted into Taxus cells.

Genetically modified Taxus cells were obtained and tested for paclitaxel precursors.

Methods and media were developed to successfully scale up plant cells to 50L.

Outcome

This project provides a technical route to enhance paclitaxel production in Taxus VSCs, which would facilitate the establishment of a high-performance biomanufacturing platform in paclitaxel production at Green Bioactives.

The technology readiness level moved from 3 to 7.

The impact and outcome of this project will contribute to Green Bioactives’ fundraising which may potentially create 5 – 10 new jobs by 2024 and 10 – 15 further new jobs by 2026.