Genetic and chemical characterisation of the cornexistin pathway provides further insight into maleidride biosynthesis

Abstract

The biosynthesis of the herbicide cornexistin in the fungus Paecilomyces variotii was investigated by full sequencing of its genome, knockout of key genes within its biosynthetic gene cluster and isolation and identification of intermediate compounds. The general biosynthetic pathway resembles that of byssochlamic acid and other nonadrides in the early stages, but differs in requiring fewer enzymes in the key nonadride dimerisation step, and in the removal of one maleic anhydride moiety.

Uncovering biosynthetic relationships between antifungal nonadrides and octadrides

“…3). Enhancement of C-5 in the 13 C NMR spectrum was observed, but there was no coupling to an adjacent 13 C, indicating that it originates from a cleaved acetate and therefore that a carbon atom is lost during zopellin biosynthesis.…”

“…5, 10 castaneiolide 6, 11 rubratoxins, e.g. 7 12 and cornexistin 8, 3,13 the octadride viburspiran 9 and more recently two heptadrides agnestadrides A 10 and B have been isolated from Byssochlamys fulva. 14 In certain cases the relative and absolute stereochemistry of the maleidrides remain unknown, and various details of their biosynthesis are yet to be fully elucidated.…”

Oryzines A & B, Maleidride Congeners from Aspergillus oryzae and Their Putative Biosynthesis

“…The structures of the oryzines indicate a biosynthetic relationship to the maleidrides [ 6 , 26 , 27 ]. In general, the biosynthesis of maleidrides is characterized by condensation of an acyl CoA thiolester of variable chain-length with oxaloacetic acid, catalyzed by a citrate synthase (CS).…”

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“…13 The biosynthetic pathway of the herbicide cornexistin 28 in the fungus Paceilomyces variotii has been characterised using a combination of genome sequencing, gene knockout and isolation of the resulting intermediates. 17 The early stages of the cornexistin pathway resembles other nonadrides but requires fewer enzymes for later steps such as nonadride dimerisation. The biosynthetic pathway of azaphilone pigments such as rubropunctatin 29 has been elucidated in Monascus ruber M7.…”