1,3,6,8-tetrahydroxynaphthalene reductase (T4HNR) (T4HNR)

1,3,6,8-tetrahydroxynaphthalene reductase (T4HNR) is a key enzyme in the dihydroxynaphthalene (DHN) melanin biosynthetic pathway of various pathogenic fungi, most notably Magnaporthe oryzae, the causative agent of rice blast disease (UniProt P30331). It catalyzes the NADPH-dependent reduction of 1,3,6,8-tetrahydroxynaphthalene to scytalone and 1,3,8-trihydroxynaphthalene to vermelone (PubMed: 1455900). Melanin is essential for the structural integrity and function of the fungal appressorium, providing the mechanical pressure necessary to penetrate the host plant epidermis (PubMed: 10459170). By inhibiting T4HNR, fungicides like tricyclazole and pyroquilon prevent melanin deposition, thereby rendering the fungus unable to infect the host (PubChem CID 5523). This enzyme is a member of the short-chain dehydrogenase/reductase (SDR) family and is a validated target for agricultural crop protection (PubMed: 11744303). The inhibition of this pathway is a non-fungitoxic mechanism, meaning it prevents disease without necessarily killing the fungal cells, which can reduce the selection pressure for resistance (PubMed: 12147477). However, resistance has been observed in field populations, often linked to mutations in the gene encoding the reductase (PubMed: 15643757). T4HNR is highly conserved among many ascomycete fungi that utilize the DHN-melanin pathway for virulence (PubMed: 16460375). Structural studies have revealed the binding mode of inhibitors like tricyclazole within the active site, facilitating the design of next-generation fungicides (PubMed: 1455900). Overall, T4HNR remains a critical target for managing devastating crop diseases globally.

Other names

Tetrahydroxynaphthalene reductaseTHR11,3,6,8-THN reductaseT4HN reductase

Inhibition of the NADPH-dependent reduction of 1,3,6,8-tetrahydroxynaphthalene to scytalone, which prevents the synthesis of DHN-melanin required for fungal appressorial penetration of host plants (PubMed: 1455900).