Biosynthesis of spathulenol and camphor stand as a competitive route to artemisinin production as revealed by a new chemometric convergence approach based on nine locations’ field-grown Artemesia annua L.

Abstract Since isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP) are the universal precursors of both essential oil components, and the antimalarial agent artemisinin and its derivatives in Artemesia annua L., this paper aims to correlate the spotted differences in their concentrations by screening Artemesia annua L. field-grown in nine locations around the world that may reveal the role of any these compounds as precursors or competitors in the biosynthetic pathway of the sesquiterpene lactone : artemisinin. Principal component analysis (PCA) revealed that artemisinin is positively correlated to β-pinene, 1,8-cineole, sabinene hydrate, borneol and 1-octen-3-ol; but negatively to artemisinic acid and β-caryophyllene oxide. Hierarchical cluster analysis (HCA) classified locations into two distinct groups in which artemisinin concentration stood as the main driving factor to build similarities between the locations. In parallel, an improved convergence approach based on idiosyncratic similarities able to capture heterogeneity across individuals is proposed, which was able to classify compounds into four distinct clusters. Artemisinin appeared to be cross-linked to p-cymene, cis-carvyle acetate, 4-terpinene-1-ol, β-caryophyllene, β-farnesene, β-selinene, α-selinene, β-caryophyllene oxide and α-costol. It is interesting to see how camphor and spathulenol behaved as a distinct cluster group, which suggests that biosynthesis of these two compounds follows a different but a competitive pathway ; thus limiting their production could be a key to control and enhance the production of artemisinin.