Identification and Characterization of a Cryptic Bifunctional Type I Diterpene Synthase Involved in Talaronoid Biosynthesis from a Marine-Derived Fungus

Abstract

We report the identification of the <i>tnd</i> biosynthetic cluster from the marine-derived fungus <i>Aspergillus flavipes</i> and the in vivo characterization of a cryptic type I diterpene synthase. The heterologous expression of the bifunctional terpene synthase led to the discovery of a diterpene backbone, talarodiene, harboring a benzo[<i>a</i>]cyclopenta[<i>d</i>]cyclooctane tricyclic fused ring system. The conversion of geranylgeranyl diphosphate to talarodiene was investigated using ¹³C-labeling studies, and stable isotope tracer experiments showed the biotransformation of talarodiene into talaronoid C.