RESUMEN
Xenovulene A is a complex fungal meroterpenoid, produced by the organism hitherto known as Acremonium strictum IMI 501407, for which limited biosynthetic evidence exists. Here, we generate a draft genome and show that the producing organism is previously unknown and should be renamed as Sarocladium schorii. A biosynthetic gene cluster is discovered which bears resemblance to those involved in the biosynthesis of fungal tropolones, with additional genes of unknown function. Heterologous reconstruction of the entire pathway in Aspergillus oryzae allows the chemical steps of biosynthesis to be dissected. The pathway shows very limited similarity to the biosynthesis of other fungal meroterpenoids. The pathway features: the initial formation of tropolone intermediates; the likely involvement of a hetero Diels-Alder enzyme; a terpene cyclase with no significant sequence homology to any known terpene cyclase and two enzymes catalysing oxidative-ring contractions.
Asunto(s)
Vías Biosintéticas/genética , Enzimas/metabolismo , Proteínas Fúngicas/metabolismo , Hypocreales/metabolismo , Sesquiterpenos/metabolismo , Aspergillus oryzae/genética , Aspergillus oryzae/metabolismo , Reacción de Cicloadición , Enzimas/genética , Proteínas Fúngicas/genética , Genes Fúngicos/genética , Hypocreales/genética , Familia de Multigenes/genética , Secuenciación Completa del GenomaRESUMEN
Covering: 1893 to 2017Harold Raistrick was involved in the discovery of many of the most important classes of fungal metabolites during the 20th century. This review focusses on how these discoveries led to developments in isotopic labelling, biomimetic chemistry and the discovery, analysis and exploitation of biosynthetic gene clusters for major classes of fungal metabolites including: alternariol; geodin and metabolites of the emodin pathway; maleidrides; citrinin and the azaphilones; dehydrocurvularin; mycophenolic acid; and the tropolones. Key recent advances in the molecular understanding of these important pathways, including the discovery of biosynthetic gene clusters, the investigation of the molecular and chemical aspects of key biosynthetic steps, and the reengineering of key components of the pathways are reviewed and compared. Finally, discussion of key relationships between metabolites and pathways and the most important recent advances and opportunities for future research directions are given.