.png){kind=icon}
.png){kind=icon}
Return
Indole Ring Expansion and Rearrangement-Enabled Quinoline Scaffold Formation in the Biosynthesis of the Antitumor Monoterpene Indole Alkaloid Camptothecin
.png){kind=icon}
PRE
AI
Y
S
Y
Y
DOI：10.1021/acschembio.6c00105.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Camptothecin (CAM), a well-known complex plant antitumor monoterpene indole alkaloid (MIA) with a unique pyrroloquinoline scaffold, is structurally and biosynthetically distinct from indole-type MIAs. Strictosamide (STM), a glucosylated indole-type MIA with a 6/5/6/6/6 pentacyclic scaffold, is the penultimate biosynthetic intermediate for CAM biosynthesis. Herein, we report the indole ring expansion and rearrangement of STM, rings BC opening (C2–C7 double bond cleavage), and subsequent C2–C6 double bond formation for rings BC reclosure, generating pumiloside (PUM), an MIA with a 6/6/5/6/6 framework featuring a quinoline moiety. Flavins such as flavin mononucleotide or sunlight were demonstrated to catalyze the skeletal conversion of STM to PUM. The flavin- or photocatalyzed indole ring expansion and rearrangement could be applied to a series of indole-type MIAs, producing the corresponding quinoline-containing MIAs. The present study bridged the biosynthetic gap between the indole-containing 6/5/6/6/6 pentacyclic framework and the quinoline-containing 6/6/5/6/6 pentacyclic scaffold that is involved in CAM biosynthesis. The described indole ring expansion and subsequent rearrangement enabled an alternative for ring expansion of a variety of indole-type MIAs, leading to a series of quinoline-containing complex alkaloids.
Keywords:
Biosynthesis
High-performance liquid chromatography
Organic compounds
Peptides and proteins
Scanning tunneling microscopy
Journal
IF:
3.8
Papers:
5.4K
Citations:
1.7W
Organization
Cited Papers