Genome Mining for Sesterterpenes Using Bifunctional Terpene Synthases Reveals a Unified Intermediate of Di/Sesterterpenes

Ying Ye, Atsushi Minami, Attila Mandi, Chengwei Liu, Tohru Taniguchi, Tomohisa Kuzuyama, Kenji Monde, Katsuya Gomi, Hideaki Oikawa

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

Genome mining is a promising method to discover novel secondary metabolites in the postgenomic era. We applied the Aspergillus oryzae heterologous expression system to functionally characterize cryptic bifunctional terpene synthase genes found in fungal genomes and identified the sesterfisherol synthase gene (NfSS) from Neosartorya fischeri. Sesterfisherol contains a characteristic 5-6-8-5 tetracyclic ring system and is modified by cytochrome P450 monooxygenase (NfP450) to sesterfisheric acid. The cyclization mechanism was proposed on the basis of the analysis of in vivo and in vitro enzymatic reactions with isotopically labeled precursors. The mechanism involves C1 cation-olefin IV-olefin V cyclization followed by five hydride shifts, allowing us to propose a unified biogenesis for sesterterpenes branching from bicyclic (5-15), tricyclic (5-12-5), and tetracyclic (5-6-8-5) cation intermediates. Furthermore, the mechanism is distinct from that of a separate class of di/sesterterpenes including fusicoccins and ophiobolins. The difference between mechanisms is consistent with phylogenetic analysis of bifunctional terpene synthases, suggesting that the amino acid sequence reflects the initial cyclization mode, which is most likely related to the initial conformation of a linear prenyl diphosphate.

Original languageEnglish
Pages (from-to)11846-11853
Number of pages8
JournalJournal of the American Chemical Society
Volume137
Issue number36
DOIs
Publication statusPublished - 2015 Sep 16

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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