Discovery of (±)‐Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase

Abstract: (±)‐Penindolenes A−D (1–4), the first representatives of indole terpenoids featuring a γ‐lactam skeleton, were isolated from the mangrove‐derived endophytic fungus Penicillium brocae MA‐231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ‐lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3‐cleavage of the indole ring to generate two keto groups in 1. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase‐like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Discovery of (±)‐Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase ; day:21 ; month:05 ; year:2024 ; extent:9 ; Angewandte Chemie / International edition. International edition ; (21.05.2024) (gesamt 9)

Beteiligte, Orts- und Zeitangaben

• Urheber: Meng, Ling‐Hong ; Awakawa, Takayoshi ; Li, Xiao‐Ming ; Quan, Zhiyang ; Yang, Sui‐Qun ; Wang, Bin‐Gui ; Abe, Ikuro

Weitere Informationen

• DOI: 10.1002/anie.202403963
• URN: urn:nbn:de:101:1-2405221412443.814615429732
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:47 MESZ