The Genetic Map of Artemisia annua L. Identifies Loci Affecting Yield of the Antimalarial Drug Artemisinin

Abstract

Artemisinin is a plant natural product produced by Artemisia annua and the active ingredient in the most effective treatment for malaria. Efforts to eradicate malaria are increasing demand for an affordable, high-quality, robust supply of artemisinin. We performed deep sequencing on the transcriptome of A. annua to identify genes and markers for fast-track breeding. Extensive genetic variation enabled us to build a detailed genetic map with nine linkage groups. Replicated field trials resulted in a quantitative trait loci (QTL) map that accounts for a significant amount of the variation in key traits controlling artemisinin yield. Enrichment for positive QTLs in parents of new high-yielding hybrids confirms that the knowledge and tools to convert A. annua into a robust crop are now available.

Artemisia annua mutant impaired in artemisinin synthesis demonstrates importance of nonenzymatic conversion in terpenoid metabolism

“…We used the TILLING method (28) to screen for mutations in the single-copy (Fig. S1) CYP71AV1 gene in an F2 population of A. annua that had been derived from an ethyl methane sulfonate (EMS)-mutagenized population of the Artemis F1 hybrid, as described (19). This process resulted in an allelic series of 10 mutants, of which just 1 was nonsense because of a G-to-A transition in the second exon of CYP71AV1 (Fig.…”

“…This latter class, of which artemisinin is a member, are typically bioactive and therefore potential targets for development as pharmaceuticals (22). Consistent with their phytochemical complexity, it is known that glandular secretory trichomes express multiple members of gene families, encoding enzymes of specialized metabolism, including terpene synthases and cytochrome P450 oxidases (16,19,23). Many of these enzymes are considered to be promiscuous (24).…”

“…Therefore, microbial-based "complete" synthetic biology routes to artemisinin may never be achievable. Meanwhile, modern molecular breeding has succeeded in improving A. annua (19), creating hybrids reaching artemisinin yields of 1.4% dry leaf biomass in commercial field trials (20) (www.artemisiaf1seed.org/).…”

OSC2 and CYP716A14v2 Catalyze the Biosynthesis of Triterpenoids for the Cuticle of Aerial Organs of Artemisia annua

“…As the full-length coding regions of OSC2 and the candidate P450s CY-P704A87 and CYP81B58 were not present in the assembled RNA-seq data set of Soetaert et al (2013), additional A. annua RNA-seq data were downloaded from the NCBI Short Read Archive (accession number SRA009227; Graham et al, 2010), and the FASTQ files containing the read sequences and quality scores were extracted using the NCBI SRA Toolkit version 2.1.7. The reads were quality filtered and assembled using default settings of the CLC Genomics Workbench 4.8.…”

Chitosan oligosaccharide and salicylic acid up-regulate gene expression differently in relation to the biosynthesis of artemisinin in Artemisia annua L.

“…The sesquiterpene lactone peroxide artemisinin is the major bioactive compound in A. annua, and currently artemisinin-based combination therapy is the most popular treatment method against malaria [1]. In addition to the antimalarial effect, the anticancer activity of artemisinin and its activity against other parasite species has been demonstrated.…”