Genome-based deletion analysis in Aspergillus terreus reveals the acetylaranotin bis-thiomethyltransferase gene

Acetylaranotin is an epipolythiodiketopiperazine (ETP) secondary metabolite with a broad range of bioactivities. We demonstrated that ATEG_01465.1 located outside of acetylaranotin gene cluster is responsible for catalyzing the S-methylation of its biosynthetic pathway. Combining the previous characterization of acetylaranotin biosynthetic gene cluster together with the identification of its S-methyltransferase provides a means to obtain second-generation acetylaranotin derivatives previously inaccessible. By permutations of targeted deletions of ATEG_01465.1, acetyltransferase (AtaH), and benzoate hydroxylase (AtaY), three novel acetylaranotin derivatives were produced by Aspergillus terreus.