Root regulation of artemisinin production in Artemisia annua: trichome and metabolite evidence

Abstract

Roots of plants with high artemisinin-producing leaves increased leaf production of artemisinin in low-producing plants and vice versa indicating roots are involved in controlling artemisinin biosynthesis in shoots. The anti-malarial sesquiterpene, artemisinin, is produced and stored in glandular trichomes (GLTs) of Artemisia annua. Evidence suggested roots, which produce no significant artemisinin nor precursor compounds, regulate production of artemisinin biosynthesis in the leaves. Using grafting, we studied the relationship between rootstock and scion by measuring GLTs and five artemisinic metabolites (artemisinin, deoxyartemisinin, dihydroartemisinic acid, artemisinic acid, arteannuin B) in scions of ungrafted, self-grafted, and cross-grafted plants among three cultivars: S and 15 both having GLTs with artemisinin at 1.49 and 0.57 %, respectively, and G producing neither GLTs nor detectable artemisinin. All artemisinin-producing self-grafts, e.g., S/S (scion/rootstock) and 15/15, produced more artemisinin than ungrafted plants, likely from grafting stress. S/S grafts also produced more GLTs. The 15/S grafts produced more artemisinin than S/15, suggesting rootstocks from high producing S plants stimulated artemisinin production in 15 scions. S/15 grafts yielded less artemisinin than S/S, but more than either 15/15 or ungrafted n15 and nS; S/15 grafts also had a lower density of GLTs than S/S, suggesting rootstock inhibition of the scion. The S rootstock induced trace artemisinin production in G scions, but did not induce GLT formation in G/S grafts. Different grafts exhibited different trichome morphologies and effects on artemisinic pathway flux. This study provides new information regarding the role of roots in GLT development and artemisinin production in this important medicinal plant.

Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches

“…Various attempts were made to increase the number of glandular trichomes and in one such study the expression of β glucosidase ( bgl1 ) gene in A. annua through Agrobacterium -facilitated transformation resulted in 66% and 20% increase in the number of glandular trichomes on flowers and leaves, respectively, which in turn resulted in 2.56% and 1.4% (w/w) increase in artemisinin (Singh et al 2016 ). More recently, using an A. annua mutant (glandless, GLS) that produces no glandular trichomes and no detectable artemisinin (Duke et al 1994 ), non-glandular T-trichomes found in this species also produced detectable artemisinin (Wang et al 2016 ; Judd et al 2019 ) as further detailed in Sect. 2.6.…”

“…These results were corroborated by Nguyen et al ( 2013 ) who showed that rooted shoots increased their artemisinin level mainly by enlarging the glandular trichomes, but not by increasing their number. In a follow-up study, Wang et al ( 2016 ) used the glandless A. annua mutant (GLS) in grafting studies. GLS produces no glandular trichomes and no detectable artemisinin (Duke et al 1994 ).…”

Artemisinin Biosynthesis in Non-glandular Trichome Cells of Artemisia annua

“…To further understand artemisinin biosynthesis in non-GT cells, we applied all the above-mentioned approaches to analyze the reported glandless (gl) mutant of A. annua, which lacks GTs and artemisinin (Duke et al, 1994;Wang et al, 2016). The gl plantlets (Figure 7A) were regenerated via micropropagation.…”

Biotechnological approaches for artemisinin production in Artemisia

“…Another study conducted on A. annua suggests roots (which neither produce significant artemisinin nor its precursor compounds) to regulate artemisinin production in the leaves. Researchers grafted roots of lines with high artemisinin-producing leaves to the low artemisinin producing shoots and observed an increased leaf production of artemisinin in those low artemisinin-producing plants (Wang et al 2016 ). A wide range of various reports describing the A&D production and its uses is given below.…”