INHIBIT MOSQUITO PHENOL OXIDASE ACTIVITY BY NATURALLY OCCURING ENDOGENOUS DOPA

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Anopheles gambiae and Aedes albopictus are medically important mosquito vectors. The development of new strategies for the control of these and other vector species of mosquitoes is an important element of disease control. Phenol oxidase (PO; or tyrosinase) is an important copper containing enzyme responsible for a casade of events which leads to the production of melanin. This enzyme plays an important role in insect development and is a vital component of the immune system. Recently, Tuskamoto et al (BBRC 184 86, 1992) described a novel potent endogenous dopa-containing inhibitor of phenol oxidase from Musca domestica (common housefly). Following this scientific breakthrough, we developed a collaboration with Dr. Tuskamoto to similarly investigate POI in two genetically divergent mosquito species. Our initial results suggest that Aedes albopictus (Asian Tiger mosquito; also the #1 nuisance-biting mosquito in in Louisiana) contains a fairly high PO activity with a higher affinity (Km=0.8 mM) towards dopa than that of the housefly enzyme (Km=2.7~4.0 mM). Phenoloxidase inhibitor (POI) isolated from housefly pupae is able to inhibit housefly PO in a competitive manner (Ki=10~20 nM). In contrast, inhibition of mosquito PO by housefly POI was noncompetitive and the affinity of housefly POI towards the mosquito PO was much lower (Ki=20 uM). We evaluating PO activity of Anopheles gambiae and beginning to purify endogenous mosquito POIs. This research to characterize POI in mosquitoes could potentially lead to novel and commercially viable products for mosquito control (as is being done currently with POIs of houseflies).