The Regulatory Mechanism of Cytochrome P450 Family Proteins under Azole Resistance in Neurospora Crassa

: The azoles are the most widely used antifungal drugs. Their target ERG-11 and its downstream protein ERG-5 play significant roles in resistance to the azoles. Both of them belong to the cytochrome P450 family proteins. Except them, there are many other P450 family proteins, but their contribution to fungal drug-resistance is not clear. In this research, we analyzed the effects of cytochrome P450 family proteins on fungal drug-resistance to azoles using the model filamentous fungus N. crassa as research material. Through the azole susceptibility test to the knockout mutants of 18 P450 family proteins including ERG-5, we found that the other 17 P450 family proteins except ERG-5, have the similar susceptibility to azole drugs to the wild-type. Furthermore, we determined the sensitivity of these knockout mutants to benzoic acid, and screened a sensitive mutant to that drug. The corresponding gene (NCU08128) encodes a phenyl-4-monooxygenase.We further analyzed the possible mechanism of the sensitivity of this gene to benzoic acid. We confirmed the roles of the other cytochrome P450 family proteins except ERG-11 and ERG-5in fungal resistance to azole drugs, using the model filamentous fungus N. crassaas research material. The above researches enriched the drug resistance mechanism of filamentous fungi and provided new targets for the development of novel antifungal drugs.