Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
The Biosynthesis of Norsesquiterpene Aculenes Requires Three Cytochrome P450 Enzymes to Catalyze a Stepwise Demethylation Process
Ist Teil von
Angewandte Chemie (International ed.), 2019-12, Vol.58 (51), p.18414-18418
Auflage
International ed. in English
Ort / Verlag
Germany: Wiley Subscription Services, Inc
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Aculenes are a unique class of norsequiterpenes (C14) that are produced by Aspergillus aculeatus. The nordaucane skeleton in aculenes A–D may be derived from an ent‐daucane precursor through demethylation, however, the enzymes involved remain unexplored. We identified the biosynthetic gene cluster and characterized the biosynthetic pathway based on gene inactivation, feeding experiments, and heterologous reconstitution in Saccharomyces cerevisiae and Aspergillus oryzae. We discovered that three cytochrome P450 monoxygenases are required to catalyze the stepwise demethylation process. AneF converts the 12‐methyl group into a carboxylic acid and AneD installs the 10‐hydroxy group for later tautomerization and stabilization. Finally, AneG installs an electron‐withdrawing carbonyl group at the C‐2 position, which triggers C‐12 decarboxylation to yield the nordaucane skeleton. Additionally, a terpene cyclase (AneC) was found that forms a new product (dauca‐4,7‐diene).
Long time no C: Aculenes are a class of norsesquiterpenes (C14) that are derived from daucane sesquiterpenes (C15), but the biosynthetic basis of the demethylation remained unknown. Three novel P450 monooxygenases were discovered to catalyze a stepwise demethylation process, and a new ent‐daucane cyclase was also discovered. This work sheds light on how nature performs enzymatic demethylation and reveals new tools to expand chemical diversity.