Redox Enzymes Required for Construction of the Ergot Alkaloid Framework

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The ergot alkaloids, which are found in hundreds of fungal and plant species, exhibit a variety of biological activities that have ramifications for both the medicinal and agricultural industries. Understanding the biosynthetic pathways that generate these compounds will allow exploitation of ergots for a wider variety of applications. Furthermore, the biochemical transformations involved in these pathways are unprecedented, and we anticipate that these enzymes may be used outside of the ergot pathway for other biotechnological applications. For example, numerous bio-industrial applications have been reported for Old Yellow Enzyme homologs and we envision that the work described in Objective 1 will ultimately enable the development of more versatile Old Yellow Enzyme catalysts. All ergot alkaloids contain a common 4-ring scaffold, called the ergoline ring system. The enzymology of ergoline ring formation is still unclear, and sophisticated chemical techniques for synthesis of substrates and structural elucidation of enzymatic products is required. A multi-disciplinary team that has the capacity for molecular biology and enzymology, as well as a fundamental understanding of the complex redox chemistry involved, is needed to unlock the potential harbored within the ergot alkaloid biosynthetic pathway

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