| Camptothecin is an important anticancer drug produced by Camptotheca acuminata. As part of an investigation into camptothecin's biosynthesis, the enzyme 10-hydroxygeraniol oxidoreductase (10HGO) was isolated and characterized. 10HGO is involved early in the biosynthesis of camptothecin where it oxidizes 10-hydroxygeraniol to 10-oxogeranial. 10HGO activity is usually only detectable in plants that produce iridoids (a group of secondary metabolites which includes camptothecin), yet 10HGO displays 70--84% sequence similarity with various zinc-containing long chain alcohol dehydrogenases found in most plants. The zinc-containing long chain alcohol dehydrogenases that are highly similar to 10HGO are BADs (Benzyl alcohol dehydrogenases), CADs (Cinnamyl alcohol dehydrogenases), MTDs (Mannitol dehydrogenases), and SADs (Sinapyl alcohol dehydrogenases). A phylogram constructed from these protein sequences shows that 10HGOs are the most closely related to MTDs. However, neither 10HGO's substrate specificity nor regulation match that of MTD or any other of the known zinc-containing long chain alcohol dehydrogenases. These results suggest that 10HGO has evolved (or is evolving) from the same ancestral protein as these other zinc-containing long chain alcohol dehydrogenases to carry out its new role in camptothecin biosynthesis. |
