BIOSYNTHESIS OF ERGOT ALKALOIDS

点击翻译按钮获取中文摘要

The biosynthesis of the commercially important ergot alkaloids will be studied in a collaboration between a synthetic organic and a bioorganic research group. To unravel the mechanism of the closure of ring C of the ergoline system, syntheses for several potential intermediates between dimethylallytryptophan and chanoclavine-I will be developed and used to prepare isotopically labeled substrates. These will be tested in feeding and trapping experiments with cultures of the ergot fungus to establish their role in the biosynthesis. Conversions demonstrated in vivo will then be examined in cell-free extracts of the ergot fungus, and key enzymes will be purified for more detailed mechanistic studies. In addition to C-ring formation we will, at the enzymatic level, also study the cyclization of chanoclavine-I to agroclavine. A second, long-term goal of this project is the elucidation of the evolutionary relationship of the ergot alkaloid biosynthetic pathways in fungi and higher plants using a molecular genetic approach.