Functional analysis of orthologous artemisinic aldehyde Δ11(13)-reductase reveals potential artemisinin-producing activity in non-artemisinin-producing Artemisia absinthium

Abstract

Artemisinin is the most effective antimalarial compound isolated from Artemisia annua. Artemisinic aldehyde Δ11(13)-reductase (DBR2) catalyzes the reduction of artemisinic aldehyde into dihydroartemisinic aldehyde, switching the pathway towards artemisinin production. Although other Artemisia species cannot produce artemisinin, we found a putative DBR2 ortholog expressed in A. absinthium (abDBR2). We examined the catalytic activity of abDBR2 in vitro and found that it shows comparable activity to that of DBR2 based on the reduction of artemisinic aldehyde into dihydroartemisinic aldehyde. Furthermore, we found that dihydroartemisinic aldehyde was detected in the extract of A. absinthium leaves fed with artemisinic aldehyde, suggesting the presence of active abDBR2 in planta. Our results indicate that A. absinthium may be a potential host for the production of artemisinin through metabolic engineering.