Dissection of the phytohormonal regulation of trichome formation and biosynthesis of the anti-malarial compound artemisinin in Artemisia annua plants

\u2022 Biosynthesis of the sesquiterpene lactone and potent anti-malarial drug artemisinin occurs in glandular trichomes of Artemisia annua plants and is subjected to a strict network of developmental and other regulatory cues. \u2022 The effects of three hormones, jasmonate, gibberellin, and cytokinin, were studied at the structural and molecular level in two different A. annua chemotypes by microscopic analysis of gland development, and by targeted metabolite and transcript profiling. Furthermore, a genome-wide cDNA-AFLP-based transcriptome profiling was carried out of jasmonate-elicited leaves at different developmental stages. \u2022 Although cytokinin and gibberellin positively affected at least one aspect of gland formation, these two hormones did not stimulate artemisinin biosynthesis. Only jasmonate simultaneously promoted gland formation and coordinated transcriptional activation of biosynthetic gene expression, which ultimately lead to increased sesquiterpene lactone accumulation with chemotype-dependent effects on the distinct pathway branches. Transcriptome profiling revealed a trichome-specific fatty acyl-CoA reductase, TFAR1, the expression of which correlates with trichome development and sesquiterpene biosynthesis. \u2022 TFAR1 is potentially involved in cuticular wax formation during glandular trichome expansion in leaves and flowers of A. annua plants. Analysis of phytohormone-modulated transcriptional regulons provides clues to dissect the concerted regulation of metabolism and development of plant trichomes.Peer reviewed: YesNRC publication: Ye