Investigations into the biosynthesis of the antifungal strobilurins

Iqbal, Zafar; Han, Li‐Chen; Soares-Sello, Anna M.; Nofiani, Risa; Thormann, Gerald; Zeeck, Axel; Cox, Russell J.; Willis, Christine L.; Simpson, Thomas J.

doi:10.1039/c8ob00608c

Cited by 21 publications

(21 citation statements)

References 37 publications

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“…The proposed rearrangement mechanism involves the unusual migration of a carboxylate as proven by the isotopic labelling studies 10 . Similar processes are known, for example, during the mechanism of methylmalonate mutase and during the biosynthesis of the tropane alkaloid hyoscyamine from littorine 28 (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…Isotopic feeding experiments have shown that strobilurin A 1 10 and oudemansin A 2 11 are polyketides, unusually derived from a benzoate starter unit derived by the degradation of phenylalanine via cinnamate. In fungi, polyketides are produced by iterative polyketide synthase (PKS) enzymes that extend acyl coenzyme A (CoA) starter units using decarboxylative Claisen-type reactions with malonyl CoA 12 .…”

Section: Introductionmentioning

confidence: 99%

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Strobilurin biosynthesis in Basidiomycete fungi

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Strobilurin biosynthesis in Basidiomycete fungi

et al. 2018

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“…The choice of reductant proved to be critical with regard to the final geometry of the double bond. For instance, triethylsilane and methyl formate gave E / Z ratios of 2:1 and 2.5:1, respectively. More promising results for the generation of the desired ( E )‐isomer were obtained using triethylammonium formate .…”

Section: Resultsmentioning

confidence: 99%

Towards the Sarpagine‐Ajmaline‐Macroline Family of Indole Alkaloids: Enantioselective Synthesis of an N‐Demethyl Alstolactone Diastereomer

Dagoneau

Wang

2020

Chemistry A European J

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the strategy involving the use of functionalized tetrahydro‐6H‐cycloocta[b]indol‐6‐one is reported as a key intermediate for synthesis of members of the sarpagine‐ajmaline‐macroline family of monoterpene indole alkaloids. The desired tricycle was synthesized through the following key steps: 1) Evans’ syn‐selective aldolization; 2) Liebeskind–Srogl cross‐coupling using the phenylthiol ester of 3‐chloropropanoic acid as a surrogate of acrylic thioester for the synthesis of 2,3‐disubstituted indoles; and 3) ring‐closing metathesis (RCM) for the formation of the eight‐membered ring. An N‐allylation followed by intramolecular 1,4‐addition was planned for synthesis of the vobasine class of natural products. However, attempted cyclizations under a diverse set of conditions involving anionic, radical, and organopalladium/organonickel species failed to produce the bridged ring system. On the other hand, esterification of the pendant primary alcohol function with acetoacetic acid, followed by intramolecular Michael addition, afforded the desired tetracycle with excellent diastereoselectivity. Subsequent functional group manipulation and transannular cyclization of the amino alcohol afforded the N(1)‐demethyl‐3,5‐diepi‐alstolactone. We believe that the same synthetic route would afford the alstolactone should the amino alcohol with appropriate stereochemistry be used as the starting material.

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“…6 Isotopic feeding experiments showed that strobilurin A 1 is a polyketide. 8 The biosynthetic steps to strobilurin A 1 have been reported recently by our group (Scheme 1). 6 Genome sequencing of S. tenacellus and S. lutea revealed that each organism harboured a biosynthetic gene cluster (BGC) responsible for the production of 1.…”

Section: Introductionmentioning

confidence: 95%