Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

Chengwei Liu, Koichi Tagami, Atsushi Minami, Tomoyuki Matsumoto, Jens Christian Frisvad, Hideyuki Suzuki, Jun Ishikawa, Katsuya Gomi, Hideaki Oikawa

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Penitrem A is one of the most elaborated members of the fungal indole diterpenes. Two separate penitrem gene clusters were identified using genomic and RNA sequencing data, and 13 out of 17 transformations in the penitrem biosynthesis were elucidated by heterologous reconstitution of the relevant genes. These reactions involve 1) a prenylation‐initiated cationic cyclization to install the bicyclo[3.2.0]heptane skeleton (PtmE), 2) a two‐step P450‐catalyzed oxidative processes forming the unique tricyclic penitrem skeleton (PtmK and PtmU), and 3) five sequential oxidative transformations (PtmKULNJ). Importantly, without conventional gene disruption, reconstitution of the biosynthetic machinery provided sufficient data to determine the pathway. It was thus demonstrated that the Aspergillus oryzae reconstitution system is a powerful method for studying the biosynthesis of complex natural products.
    Original languageEnglish
    JournalAngewandte Chemie
    Volume54
    Issue number19
    Pages (from-to)4840-5844
    Number of pages5
    ISSN0044-8249
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Biosynthesis
    • Heterologous expression
    • Indole diterpenes
    • Natural products
    • Penitrem

    Cite this

    Liu, C., Tagami, K., Minami, A., Matsumoto, T., Frisvad, J. C., Suzuki, H., Ishikawa, J., Gomi, K., & Oikawa, H. (2015). Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem. Angewandte Chemie, 54(19), 4840-5844. https://doi.org/10.1002/ange.201501072