@PhdThesis{diss_mods_00011041,
  author = 	{Wang, Linzhu},
  title = 	{Molekulare Identifizierung und Charakterisierung der Flavin-abh{\"a}ngigen Monooxygenasen in verschiedenen Pyrrolizidin-Alkaloid-adaptierten Insekten},
  year = 	{2013},
  publisher = 	{Christian-Albrechts-Universit{\"a}t zu Kiel},
  address = 	{Kiel},
  keywords = 	{Evolution; Biochemische {\"O}kologie; Flavin-abh{\"a}ngige Monooxygenase; Pyrrolizidin-Alkaloide; Insekten; Arctia caja; Danaus plexippus; Grammia geneura; Zonocerus variegatus; Tyria jacobaeae},
  abstract = 	{Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their
own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the
holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine
alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their
respective N-oxide, enabling the insects to avoid high concentrations of toxic pyrrolizidine alkaloids in the hemolymph. We
have identified a pyrrolizidine alkaloid N-oxygenase, which is a flavin-dependent monooxygenase, of the grasshopper
Zonocerus variegatus. After heterologous expression in E. coli, this enzyme shows high specificity for pyrrolizidine alkaloids
of various structural types and for the tropane alkaloid atropine as substrates, a property that has been described previously
for a pyrrolizidine alkaloid N-oxygenase of the arctiid moth Grammia geneura. Phylogenetic analyses of insect flavin-
dependent monooxygenase sequences suggest that independent gene duplication events preceded the establishment of
this specific enzyme in the lineages of the grasshoppers and of arctiid moths. Two further flavin-dependent
monooxygenase sequences have been identified from Z. variegatus sharing amino acid identities of approximately 78{\%}
to the pyrrolizidine alkaloid N-oxygenase. After heterologous expression, both enzymes are also able to catalyze the N-
oxygenation of pyrrolizidine alkaloids, albeit with a 400-fold lower specific activity. With respect to the high sequence
identity between the three Z. variegatus sequences this ability to N-oxygenize pyrrolizidine alkaloids is interpreted as a relict
of a former bifunctional ancestor gene of which one of the gene copies optimized this activity for the specific adaptation to
pyrrolizidine alkaloid containing food plants.},
  url = 	{https://macau.uni-kiel.de/receive/diss_mods_00011041},
  file = 	{:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/dissertation_derivate_00004669/Dissertation_Wang_2013.pdf:PDF},
  language = 	{de}
}