Cell type matters: competence for alkaloid metabolism differs in two seed-derived cell strains of Catharanthus roseus

Abstract

Since the discovery of the anticancer drugs vinblastine and vincristine, Catharanthus roseus has been intensively studied for biosynthesis of several terpene indole alkaloids (TIAs). Due to their low abundance in plant tissues at a simultaneously high demand, modes of production alternative to conventional extraction are mandatory. Plant cell fermentation might become one of these alternatives, yet decades of research have shown limited success to certain product classes, leading to the question: how to preserve the intrinsic ability to produce TIAs (metabolic competence) in cell culture? We used the strategy to use the developmental potency of mature embryos to generate such strains. Two cell strains (C1and C4) from seed embryos of Catharanthus roseus were found to differ not only morphologically, but also in their metabolic competence. This differential competence became manifest not only under phytohormone elicitation, but also upon feeding with alkaloid pathway precursors. The more active strain C4 formed larger cell aggregates and was endowed with longer mitochondria. These cellular features were accompanied by higher alkaloid accumulation in response to methyl jasmonate (MeJA) elicitation. The levels of catharanthine could be increased significantly, while the concurrent vindoline branch of the pathway was blocked, such that no bisindole alkaloids were detectable. By feeding vindoline to MeJA-elicited C4 cells, vincristine became detectable; however, only to marginal amounts. In conclusion, these results show that cultured cells are not “de-differentiated”, but can differ in metabolic competence. In addition to elicitation and precursor feeding, the cellular properties of the “biomatter” are highly relevant for the success of plant cell fermentation.

Cellular concepts cure cancer

“…The contributions by Raorane et al ( 2023 ) and Lemos Cruz et al ( 2023 ) address the biosynthesis of not only vincristines, alkaloids with strong activity against leukaemia and lymphomas, but also cancers that are hard to target, such as neuroblastomas. The synthesis of these compounds is very complex and comprises around 50 enzymatic steps that are distributed over different tissues and cell types until the end product is collected in so-called idioblasts in the leaves.…”

“…However, this approach has not been successful, so far, which might be linked with the fact that it seems difficult till impossible to mimick the complex interactions between different cell types with different and complementary metabolic potencies (often termed as competence) in the leaf using a suspension culture of a single cell type. This consideration was the starting point for the work by Raorane et al ( 2023 ) addressing the competence of suspension cell strains of Catharanthus . Two strains with complementary metabolic competence were isolated from mature embryos and differed not only in morphology, but also in subcellular details, for instance mitochondrial shape.…”