Cellular and sub-cellular organisation of the monoterpenoid indole alkaloid pathway in Catharanthus roseus

Abstract

The Madagascar periwinkle (Catharanthus roseus) monoterpene indole alkaloids (MIAs), either as (hetero)dimers (vinblastine, vincristine) or as monomers (ajmalicine) are valuable pharmaceuticals with antitumoral and hypotensive properties. The biosynthetic pathway of these secondary metabolites involves several subpathways (so-called indole, methylerythritol phosphate, secoiridoid-monoterpenoids, and the MIA pathway itself). So far, 16 cDNA sequences with direct involvement in the pathway have been obtained and some additional enzymatic activities have been characterised. Metabolomic, transcriptomic and proteomic studies have revealed that this pathway presents a high degree of spatial organisation at the organ, cellular and sub-cellular levels. This paper reviews the evidence on the spatial organisation of the MIA pathway at various levels of resolution in terms of the following topics. (1) The organ-specific distribution of MIAs, related genes, related enzymes and related enzymatic activities, mainly focussing on repartition in roots versus aerial organs. (2) The cell-specific occurrence of MIA-related gene expression identified by in situ hybridisation and corresponding protein accumulation identified by immunolocalisation, with particular emphasis on the well-characterised multi-cellular compartmentation in aerial organs. In situ hybridisation revealed that the nine transcripts studied could be classified into three populations according to their position in the pathway (early-, intermediate- and late-step genes) and to their cell-specific expression patterns (internal phloem parenchyma, epidermis, laticifers/idioblasts). (3) The still poorly characterised sub-cellular localisation of MIA-related enzymes. Finally, these results are compared with the situation in other families producing other types of alkaloids, and future prospects are discussed.