2023 05: Vinca Alkaloids from Cell Cultures

Cells Need Competence

In biotechnology, cells are often called "biomass". This sounds a bit as if the nature of the cell does not matter, as long as the right gene is introduced by genetic engineering. In the real world, the individuality of the producing cell is crucial. This can be shown for medicinally relevant plant compounds that are often produced in a "team work" of several cell types, whereby each cell type drives a different, specific, chemical reaction. We have addressed this point using Catharanthus roseus, a medicinal plant from Madagascar, where we try to reconstruct the synthesis of the anti-tumour compound vincristine in cell cultures. Around 200 kg leaf material is needed for 1 mg, which makes this compound very expensive. Since the 1960ies people have tried to generate this compound in cell culture, in vain. We suspected that this different cell types need to cooperate, as it is the case in real plant tissues. In cooperatoin with the company Phyton from Ahrensburg we searched for different cell types and found two strains, Cat1 and Cat4, that activate different branches of the metabolism that are mutually exclusive and even suppressive. These cells are endowed with a quite different metabolic competence. However, when we were feeding the Cat4 cells with the precursor made from the Cat1 cells and activated defence metabolism by the stress hormone jasmonic acid, we were able, for the first time, to detect vincristine and to demonstrate by mass spectroscopy that it was really vincristine. The amounts are still very low, unfortunately, but this work shows that it is principally possible, if one more seriously considers the diversity and individuality of plant cells and their differential metabolic competence.

Publication

190. Raorane ML, Manz C, Hildebrandt S, Mielke M, Thieme A, Keller J, Bunzel M, Nick P (2023) Cell type matters: competence for alkaloid metabolism differs in two seed-derived cell strains of Catharanthus roseus. Protoplasma 260, 349-369 - pdf