Controlling a Structural Branch Point in Ergot Alkaloid Biosynthesis

JZ Cheng, CM Coyle, DG Panaccione, SE O'Connor

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The ergot alkaloids are a diverse class of fungal-derived indole alkaloid natural products with potent pharmacological activities. The biosynthetic intermediate chanoclavine-I aldehyde 1 represents a branch point in ergot biosynthesis. Ergot alkaloids festuclavine 2 and agroclavine 3 derive from alternate enzymatic pathways originating from the common biosynthetic precursor chanoclavine-I aldehyde 1. Here we show that while the Old Yellow Enzyme homolog EasA from the ergot biosynthetic gene cluster of Aspergillus fumigatus acts on chanoclavine-I aldehyde 1 to yield festuclavine 2, EasA from Neotyphodium lolii, in contrast, produces agroclavine 3. Mutational analysis suggests a mechanistic rationale for the switch in activity that controls this critical branch point of ergot alkaloid biosynthesis.
Original languageEnglish
Pages (from-to)12835-12837
Number of pages3
JournalJournal of the American Chemical Society
Volume132
Issue number37
DOIs
Publication statusPublished - 22 Sep 2010

Cite this