Fig. 10: Alternative pathway for L-DOPA incorporation to the melanin synthesis in mosquitoes.

a L-DOPA serves as a substrate for cuticular melanization via DOPAL synthase as a detoxification mechanism given a cellular redox environment that promotes L-DOPA antioxidant properties (neutral or acid pH)⁶⁶, therefore preventing its conversion to dopamine via a dopa decarboxylase. L-DOPA conversion into DOPAL leads into DOPAL buildup that promotes oligomerization and quinone adduct formation (“quinonization”) inhibiting its own metabolism and the activity of other enzymes involved in the melanin biosynthesis such as dopa decarboxylase (DDC), phenoloxidase 5 (PPO5), and dopachrome conversion enzyme (DCE)⁶⁵. b Model for dietary L-DOPA-mediated cuticular melanization proposes that Anopheles gambiae female mosquitoes use L-DOPA supplement in the sugar meal as a substrate for synthesizing cuticular melanin. L-DOPA is internalized into the midgut epithelium and exported to the hemolymph by sharing the same transporters with amino acids such as Na⁺-driven amino acid transporter, alpha2 transporter, and/or SLC protein. Within regions of flexible cuticle, in the presence of DOPAL synthase, L-DOPA is turned into DOPAL and H₂O₂ promoting oxidation of DOPAL catechol ring that results in the formation of a melanized and protective flexible cuticle via crosslinking to cuticular proteins^63,64. The contribution of gut microbiota as well as from hemocytes as key regulators of mosquito vectorial capacity and immunity, post a L-DOPA diet is under investigation. Created in BioRender. Camacho, E. (2025) https://BioRender.com/d90z642.