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- Title
Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines.
- Authors
Lai, Chen ‐ Yu; Lo, I ‐ Wen; Hewage, Ranuka T.; Chen, Yi ‐ Chen; Chen, Chien ‐ Ting; Lee, Chi ‐ Fang; Lin, Steven; Tang, Man ‐ Cheng; Lin, Hsiao ‐ Ching
- Abstract
The okaramines are a class of complex indole alkaloids isolated from Penicillium and Aspergillus species. Their potent insecticidal activity arises from selectively activating glutamate-gated chloride channels (GluCls) in invertebrates, not affecting human ligand-gated anion channels. Okaramines B (1) and D (2) contain a polycyclic skeleton, including an azocine ring and an unprecedented 2-dimethyl-3-methyl-azetidine ring. Owing to their complex scaffold, okaramines have inspired many total synthesis efforts, but the enzymology of the okaramine biosynthetic pathway remains unexplored. Here, we identified and characterized the biosynthetic gene cluster (oka) of 1 and 2, then elucidated the pathway with target gene inactivation, heterologous reconstitution, and biochemical characterization. Notably, we characterized an α-ketoglutarate-dependent non-heme FeII dioxygenase that forged the azetidine ring on the okaramine skeleton.
- Subjects
INDOLE alkaloids; PENICILLIUM; ASPERGILLUS; BIOSYNTHESIS; CHEMICAL synthesis
- Publication
Angewandte Chemie, 2017, Vol 129, Issue 32, p9606
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201705501