The Biosynthesis of Norsesquiterpene Aculenes Requires Three Cytochrome P450 Enzymes to Catalyze a Stepwise Demethylation Process. (4th November 2019)

• Record Type: Journal Article
• Authors: Lee, Chi‐Fang; Chen, Li‐Xun; Chiang, Chen‐Yu; Lai, Chen‐Yu; Lin, Hsiao‐Ching
• Is Part Of: Angewandte Chemie. Volume 131:Number 51(2019)
• Page Start: 18585
• Page End: 18589
• Publication Date: 2019-11-04
• Subjects: Biosynthese -- Cytochrom-P450-Enzyme -- Daucan -- Demethylierung -- Terpene; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201910200
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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). Abstract : Ein C weniger : Aculene sind eine von Daucan‐Sesquiterpenen (C15 ) abgeleitete Klasse von Norsesquiterpenen (C14 ), allerdings ist unbekannt, wie die Demethylierung in der Biosynthese funktioniert. Drei neu entdeckte P450‐Monooxygenasen katalysieren einen schrittweisen Demethylierungsprozess, zudem wurde eine neue ent ‐Daucancyclase entdeckt. Diese neuen Einblicke in enzymatische Demethylierung in der Natur offenbaren neue Wege zur Erweiterung chemischer Diversität.