Abstract
Strobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides. However, molecular details of the biosynthesis of strobilurins have remained cryptic. Here we report the sequence of genomes of two fungi that produce strobilurins and show that each contains a biosynthetic gene cluster, which encodes a highly reducing polyketide synthase with very unusual C-terminal hydrolase and methyltransferase domains. Expression of stpks1 in Aspergillus oryzae leads to the production of prestrobilurin A when the fermentation is supplemented with a benzoyl coenzyme A (CoA) analogue. This enables the discovery of a previously unobserved route to benzoyl CoA. Reconstruction of the gene cluster in A. oryzae leads to the formation of prestrobilurin A, and addition of the gene str9 encoding an FAD-dependent oxygenase leads to the key oxidative rearrangement responsible for the creation of the β-methoxyacrylate toxophore. Finally, two methyltransferases are required to complete the synthesis.
Highlights
Strobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides
Our results show that biosynthesis begins with construction of benzoyl coenzyme A (CoA) 16 by step-wise elimination of ammonia from phenylalanine 18, oxygenation and retro-Claisen reaction to form benzoic acid 10, which is activated to its CoA thiolester 16 by a dedicated CoA ligase
Benzoyl CoA 16 forms the starter unit for polyketide biosynthesis
Summary
Strobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides. The major class of β-methoxyacrylate agricultural fungicides were developed from the structures of 1 and 2 with the aim of increasing photo-stability and selectivity Compounds such as azoxystrobin 3 (Syngenta) and Kresoxim methyl 4 (BASF) are among the most widely used fungicides worldwide. Isotopic feeding experiments have shown that strobilurin A 110 and oudemansin A 211 are polyketides, unusually derived from a a OMe. Here we reveal the biosynthetic gene cluster (BGC) responsible for the construction of the strobilurins and reconstruct the biosynthesis of 1 in the heterologous host Aspergillus oryzae. We reveal the biosynthetic gene cluster (BGC) responsible for the construction of the strobilurins and reconstruct the biosynthesis of 1 in the heterologous host Aspergillus oryzae This reveals an unusual type of fungal PKS and the enzyme responsible for the key oxidative rearrangement reaction
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