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Controlling a structural branch point in ergot alkaloid biosynthesis

Authors :
Sarah E. O'Connor
Christine M. Coyle
Daniel G. Panaccione
Johnathan Z. Cheng
Source :
Journal of the American Chemical Society. 132(37)
Publication Year :
2010

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 homologue 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.

Details

ISSN :
15205126
Volume :
132
Issue :
37
Database :
OpenAIRE
Journal :
Journal of the American Chemical Society
Accession number :
edsair.doi.dedup.....cdcbb93b4b91f606a8b07fdd006008d8