Work

Controlling a Structural Branch Point in Ergot Alkaloid Biosynthesis

Year: 2010

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja105785p

Authors: Johnathan Z. Cheng, Christine M. Coyle, Daniel G. Panaccione, Sarah E. O’Connor

Institutions: West Virginia University, Massachusetts Institute of Technology

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G3740498208, G7469896943