Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS–PKS hybrid enzyme

Abstract

Tenuazonic acid (TeA) is a well-known mycotoxin produced by various plant pathogenic fungi. However, its biosynthetic gene has been unknown to date. Here we identify the TeA biosynthetic gene from Magnaporthe oryzae by finding two TeA-inducing conditions of a low-producing strain. We demonstrate that TeA is synthesized from isoleucine and acetoacetyl-coenzyme A by TeA synthetase 1 (TAS1). TAS1 is a unique non-ribosomal peptide synthetase and polyketide synthase (NRPS–PKS) hybrid enzyme that begins with an NRPS module. In contrast to other NRPS/PKS hybrid enzymes, the PKS portion of TAS1 has only a ketosynthase (KS) domain and this domain is indispensable for TAS1 activity. Phylogenetic analysis classifies this KS domain as an independent clade close to type I PKS KS domain. We demonstrate that the TAS1 KS domain conducts the final cyclization step for TeA release. These results indicate that TAS1 is a unique type of NRPS–PKS hybrid enzyme.

Unravelling the biosynthesis of pyriculol in the rice blast fungus Magnaporthe oryzae

“…1). Further secondary metabolites previously described to be produced by the rice blast fungus, for example, pyrichalasin H [31], pyriculol [32] or tenuazonic acid [12][13][14], were not found in this study. Based on considerations concerning the chemical structure of pyriculol, we searched for PKS-encoding genes in the genome of M. oryzae.…”

“…Additional studies have identified other metabolites produced by Magnaporthe strains, i.e. tenuazonic acid and Magtoxin [10,[12][13][14]. Tenuazonic acid is a mycotoxin synthesized by various plant pathogenic fungi.…”

“…Tenuazonic acid is a mycotoxin synthesized by various plant pathogenic fungi. The biosynthesis was hypothesized in M. oryzaefrom isoleucine and acetoacetyl-CoA by TeA synthetase 1 (TAS1) [14]. Furthermore, metabolome studies resulted in varieties of metabolites, i.e.…”

Induction of Nectriapyrone Biosynthesis in the Rice Blast Fungus Pyricularia oryzae by Disturbance of the Two‐Component Signal Transduction System

“…Melanin, a polyketide compound, is biosynthesized by the PKS ALB1/MGG_07219 and modifying enzymes . Tenuazonic acid is biosynthesized by a unique NRPS–PKS enzyme: TAS1/MGG_07803 . Pyriculols are polyketide compounds, and the identification of the pyriculol biosynthetic gene cluster containing the PKS gene MoPKS19 / MGG_10912 was reported recently .…”

“…We have previously found that knockout of the HOG MAP kinase gene OSM1 , which works downstream of the TCS, can activate the production of tenuazonic acid in P. oryzae . Herein, we show that the production of other secondary metabolites can be activated by double gene knockout of OSM1 and PoYPD1 ( MoYPD1 ), which encodes an HPt.…”