Dihydroartemisinic aldehyde

Ryden AM, Ruyter-Spira C, Quax WJ, Osada H, Muranaka T, Kayser O, Bouwmeester H (2010) The molecular cloning of dihydroartemisinic aldehyde reductase and its implication in artemisinin biosynthesis in Artemisia annua. Planta Med 76 1178-1183... 

A spectacular example of the combination of an ene reductase with other enzymatic activities is about the cascade biosynthesis of artemisinin 43 (Scheme 3.11), natural drug possessing the most rapid action against Plasmodium fcdciparum (malaria). Artemisinic acid, precursor of 43, has been produced biotedmologically on g-scale by means of an engineered yeast [68]. Then, the C(11)=C(13) bond reduction of artemisinic aldehyde 44 was catalyzed by the cloned Dbrl (double bond reductase 1) protein from Artemisia annua to yield the (llS)-dihydroartemisinic aldehyde 45 precursor. It is interesting to note that the stereochemical outcome of this ene reductase is opposite to that observed for the reduction of the very similar substrate 23 with OYEs [69]. 

ADHl-catalysis. [463] The double bond at C-11/13 is reduced by DBR2, a member of the enoate reductase family, and the aldehyde dehydrogenase ALDHl leads to the oxidation product dihydroartemisinic acid. [464] The further oxidation cascade is non-enzymatic, however stereoselective, and yields (+)-artemis-inin via relatively unstable intermediates. Geoffrey D. Brown at the University of Reading was able to demonstrate, that the Hock rearrangement of a hydroperoxide, followed by oxidation of the resulting enol with triplet oxygen, are the key steps of this sequence. [465]... 

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