title: NADP+-dependent farnesol dehydrogenase, a corpora allata enzyme involved in juvenile hormone synthesis.
abstract: The synthesis of juvenile hormone (JH) is an attractive target for control of insect pests and vectors of disease, but the minute size of the corpora allata (CA), the glands that synthesize JH, has made it difficult to identify important biosynthetic enzymes by classical biochemical approaches. Here, we report identification and characterization of an insect farnesol dehydrogenase (AaSDR-1) that oxidizes farnesol into farnesal, a precursor of JH, in the CA. AaSDR-1 was isolated as an EST in a library of the corpora allata-corpora cardiaca of the mosquito Aedes aegypti. The 245-amino acid protein presents the typical short-chain dehydrogenase (SDR) Rossmann-fold motif for nucleotide binding. This feature, together with other conserved sequence motifs, place AaSDR-1 into the "classical" NADP(+)-dependent cP2 SDR subfamily. The gene is part of a group of highly conserved paralogs that cluster together in the mosquito genome; similar clusters of orthologs were found in other insect species. AaSDR-1 acts as a homodimer and efficiently oxidizes C(10) to C(15) isoprenoid and aliphatic alcohols, showing the highest affinity for the conversion of farnesol into farnesal. Farnesol dehydrogenase activity was not detected in the CA of newly emerged mosquitoes but significant activity was detected 24 h later. Real time PCR experiments revealed that AaSDR-1 mRNA levels were very low in the inactive CA of the newly emerged female, but increased >30-fold 24 h later during the peak of JH synthesis. These results suggest that oxidation of farnesol might be a rate-limiting step in JH III synthesis in adult mosquitoes.
authors: Department of Biological Sciences, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA.
authors: Jaime G
authors: JG
authors: Mayoral
authors: Marcela
authors: M
authors: Nouzova
authors: Arti
authors: A
authors: Navare
authors: Fernando G
authors: FG
authors: Noriega
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003335:Corpora Allata / Q000201:enzymology*; D009033:Culicidae; D005204:Farnesol / Q000378:metabolism; D007313:Insecta; D007306:Insecticides; D007605:Juvenile Hormones / Q000096:biosynthesis*; D007814:Larva / Q000201:enzymology; D064430:NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; D009247:NADH, NADPH Oxidoreductases; D010084:Oxidation-Reduction; D012717:Sesquiterpenes / Q000378:metabolism
chemical_list: D007306:Insecticides; D007605:Juvenile Hormones; D012717:Sesquiterpenes; D005204:Farnesol; C036585:juvenile hormone III; D000429:Alcohol Oxidoreductases; D064430:NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; C040714:farnesol dehydrogenase; D009247:NADH, NADPH Oxidoreductases