Tetrahydroxynaphthalene reductase (THNR) (THNR)

Tetrahydroxynaphthalene reductase (THNR) is a critical enzyme in the dihydroxynaphthalene (DHN) melanin biosynthetic pathway, predominantly found in filamentous fungi (UniProt: P30101). It facilitates the NADPH-dependent reduction of 1,3,6,8-tetrahydroxynaphthalene to scytalone and 1,3,8-trihydroxynaphthalene to vermelone (PubMed: 1565937). Melanin produced through this pathway is vital for the mechanical strength of appressoria, the infection structures used by pathogens like Magnaporthe oryzae to breach plant cell walls (PubMed: 10450824). As a result, THNR is a primary target for melanin biosynthesis inhibitors (MBIs) such as tricyclazole and pyroquilon, which are used extensively in agriculture to manage rice blast (PubChem: CID 5561). Additionally, THNR is explored as a target for human fungal pathogens, where melanin serves as a virulence factor by protecting the fungus from host immune responses (PubMed: 21803878). Inhibition of THNR effectively attenuates fungal pathogenicity without necessarily being fungicidal, making it a strategic target for anti-virulence therapy. This approach reduces the selection pressure for resistance compared to traditional fungicides that target essential survival processes. The enzyme belongs to the short-chain dehydrogenase/reductase (SDR) family and requires NADPH as a cofactor for its catalytic activity (PubMed: 1565937).

Other names

1,3,6,8-tetrahydroxynaphthalene reductaseT4HNR4HNR3HNRNaphthol reductaseTrihydroxynaphthalene reductase

Inhibition of the NADPH-dependent reduction of tetrahydroxynaphthalene and trihydroxynaphthalene in the DHN-melanin biosynthetic pathway, preventing fungal penetration of host tissues.