Planta Med 2011; 77 - SL28
DOI: 10.1055/s-0031-1282151

The molecular cloning of dihydroartemisinic aldehyde reductase and its implication in artemisinin biosynthesis in Artemisia annua

O Kayser 1, A Ryden 3, H Bouwmeester 2, C Ruyter Spira 2, H Osada 4, T Muranaka 4
  • 1Technical University Dortmund, Technical Biochemistry, 44227 Dortmund, Germany
  • 2Laboratory of Plant Physiology, Wageningen University, 6700 AR Wageningen, the Netherlands
  • 3University of Groningen, Pharmaceutical Biology, 9713 AV Groningen, the Netherlands
  • 4Chemical Biology Department, Antibiotics Laboratory, Advanced Science Institute, RIKEN, 2–1, Hirosawa, Wako, Saitama 351–0198, Japan

A key point in the biosynthesis of the antimalarial drug artemisinin is the formation of dihydroartemisinic aldehyde which represents the key difference between chemotype specific pathways. This key intermediate is the substrate for several competing enzymes some of which increase the metabolic flux towards artemisinin and some of which – as we show in the present study – may have a negative impact on artemisinin production. In an effort to understand the biosynthetic network of artemisinin biosynthesis, extracts of A. annua L. flowers were investigated and found to contain an enzyme activity competing in a negative sense with artemisinin biosynthesis. The enzyme, Red1, is a broad substrate oxidoreductase belonging to the short chain dehydrogenase/reductase family with high selectivity for dihydroartemisinic aldehyde and valuable monoterpenoids. Spatial and temporal analysis of cDNA revealed Red1 to be trichome specific. The relevance of Red1 to artemisinin biosynthesis is discussed.

Figure 1: Biosynthetic pathway of artemisinin and the activity of Red1

Keywords: Artemisia annua, red1, dihydroartemisinic aldehyde, dihydroartemisinic alcohol, trichome, reductase, dehydrogenase, trichome, oxidoreductase

References: Rydén A-M, Ruyter-Spira C, Osada H, Muranaka T, Kayser O, Bouwmeester H (2010) Planta Medica 76:1–6