Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control

Trypsin-modulating oostatic factor (TMOF), a mosquito decapeptide, terminates trypsin biosynthesis in the mosquito gut. The hormone is secreted from the ovary, starting 18 h after the blood meal, circulates in the hemolymph, binds to a gut receptor and stops trypsin biosynthesis by exerting a translational control on trypsin mRNA. Because of the unique primary amino acid sequence of the hormone (YDPAPPPPPP) and its stable three-dimensional conformation, TMOF is not degraded by gut proteolytic enzymes and can traverse the gut epithelial cells into the hemolymph of adults and larvae. Using this unique property, hormone fed to different species of mosquito larvae stops food digestion and causes larval mortality. To determine the shortest amino acid sequence that can bind to the gut receptor and still cause high larval mortality, 25 analogues of TMOF were synthesized and tested. The tetrapeptide (YDPA) was as effective as the decapeptide, indicating that the binding to the gut receptor is at the N-terminus of the molecule. Cloning and expressing the hormone on the coat protein of tobacco mosaic virus (TMV) in Chlorella sp. and Saccharomyces cerevisiae cells and feeding the recombinant cells to mosquito larvae caused larval mortality. These results indicate that TMOF can be used as a new biorational insecticide against mosquito larvae.