Controlling a Structural Branch Point in Ergot Alkaloid Biosynthesis

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• 作者：Johnathan Z. Cheng ; Christine M. Coyle ; Daniel G. Panaccione ; Sarah E. O’ ; Connor
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：September 22, 2010
• 年：2010
• 卷：132
• 期：37
• 页码：12835-12837
• 全文大小：163K
• 年卷期：v.132,no.37(September 22, 2010)
• ISSN：1520-5126

文摘

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.