A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expr...
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A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.
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