Genetic Dissection of Sesquiterpene Biosynthesis by Fusarium fujikuroi

Abstract

A treasure trove of terpenes: The products of two fungal sesquiterpene synthases from the rice pathogen Fusarium fujikuroi were identified by gene-knockout experiments, genetic engineering of the fungus for production optimization, isolation of the sesquiterpenes, and structure elucidation by spectroscopic methods.

Biosynthesis of Terpenoid Natural Products in Fungi

“…It also produces a number of volatile sesquiterpenoids, and its genome contains putative sesquiterpene synthases [113]. Gene deletion studies have identified two terpene synthases responsible for the production of α-acorenol and koraiol [113]. Although α-acorenol is derived from an initial 1,6-cyclization intermediate, koraiol synthesis likely proceeds through an initial 1,11-cyclization reaction to generate a humulyl cation (Fig.…”

“…It also produces a number of volatile sesquiterpenoids, and its genome contains putative sesquiterpene synthases [113]. Gene deletion studies have identified two terpene synthases responsible for the production of α-acorenol and koraiol [113].…”

“…For example, the C-C bond formation between C1 and C11 of the primary farnesyl carbocation yields a trans-humulyl-carbocation, which is a 1,11-cyclization product. This secondary carbocation can then undergo additional cyclizations and rearrangements until carbocation quenching in the active site and subsequent release of [106,107], Pr_AS: Penicillium roqueforti (#Q03471) [84,101,108], Fs_TS: Fusarium sporotrichoides (#AAN05035) [83,109,110]; Fg_CLM1: F. graminearum (#ACY69978) [111]; Ff_sc4 & Ff_sc6: F. fujikuroi (#CCP20071 & #CCP20072 -product profiles were derived from strains containing corresponding gene knockouts) [112,113] the final sesquiterpenoid scaffold by the enzyme. Some sesquiterpene synthases catalyze first trans-cis isomerization of the 2,3-double-bond of (2E,6E)-FPP, which yields a cisoid, allylic nerolidyl-carbocation after PP i cleavage.…”

Two Histone Deacetylases, FfHda1 and FfHda2, Are Important for Fusarium fujikuroi Secondary Metabolism and Virulence

“…Noteworthy, in some cases, all cluster genes showed an altered expression pattern, while in others, only a few genes or even only one single gene of a putative cluster was affected by deletion of ffhda1. Altogether, four and six gene clusters showed differential expression under low-and highnitrogen conditions, respectively (see Table S1 in the supplemental material) (85,86). Four genes of the gibberellin gene cluster (FFUJ_14331, FFUJ_14335, FFUJ_14336, and FFUJ_14337) and four genes of the fumonisin gene cluster (FFUJ_09243, FFUJ_09246, FFUJ_09252, and FFUJ_09254) were significantly downregulated, while only one gene of the cryptic PKS13 mini-gene cluster (FFUJ_12020), consisting most likely only of one to two genes (19), was upregulated under these low-nitrogen conditions (see Table S1 in the supplemental material).…”

Volatile communication between fungi and bacteria

“…The initial products can be further converted into highly functionalised and bioactive molecules such as mycotoxins by oxidations, acylations and other modifications. In the past two decades, several fungal terpene cyclases and their related products have been characterised, including the sesquiterpene cyclases for (-)-(1R,4R,5S)-guaia-6,10(14)-diene, (+)-eremophilene, (+)-koraiol and (-)-α-acorenol from Fusarium fujikuroi (Brock et al, 2013, Burkhardt et al, 2016, longiborneol from F. graminearum (McCormick et al, 2010), trichodiene from F.…”