Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases

Takayuki Itoh, Kinya Tokunaga, Yudai Matsuda, Isao Fujii, Ikuro Abe, Yutaka Ebizuka, Tetsuo Kushiro

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indoleg-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.

Original languageEnglish
Pages (from-to)858-864
Number of pages7
JournalNature Chemistry
Volume2
Issue number10
DOIs
Publication statusPublished - 1 Oct 2010

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