Sterol inhibitor “Fluconazole” enhance the Taxol yield and molecular expression of its encoding genes cluster from Aspergillus flavipes

Abstract Taxol is a blockbuster anticancer drug that commercially synthesized from 10-decaetylbaccatin III intermediate of Taxus baccata , however, this technology has been challenged by reproducibility and association of unwanted compounds. Recently, endophytic fungi with fast growing and feasibility of molecular engineering raise the hope for sustainable production of Taxol, unfortunately the loss of their productivity with multiple subculturing is the main challenge to authenticate this approach industrially. Thus, searching for novel fungal isolates with molecular and metabolic functional stability for Taxol production was the objective of this work. Among the experimented fungal isolates, Aspergillus flavipes, a soil-dwelling saprophyte, gave the highest Taxol yield (185 µg/L). Metabolically, A. flavipes had a strong stability for Taxol production till the 10 th subcultures (185-160 µg/L) on the same cultural conditions. The yield of Taxol by A. flavipes was increased by 5 folds (850 µg/ L) with fluconazole (1.0 µg/ml) addition to 5 days old culture. The expression of Taxol biosynthetic genes ts, dbat , bapt and transcriptional factor pbcR was significantly increased by 8-10 folds upon fluconazole addition that correlates with Taxol yield. HSP70 was induced by 13 folds with addition of fluconazole to cultures of A. flavipes . Thus, Taxol biosynthesis could be transcriptionally regulated by pbcR and post-translationally modified by HSP70 chaperones. To the best of knowledge, this is the first report exploring the potency of saprophytic A. flavipes for Taxol production with metabolic stability with multiple subculturing.