This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Secondary Metabolites Biosynthesis → Nitrogen-Containing Secondary Compounds Biosynthesis → Alkaloids Biosynthesis → Indole Alkaloids Biosynthesis|
Expected Taxonomic Range: Clavicipitaceae
Ergot alkaloids are a complex family of indole derivatives with diverse structures and biological activities. They are toxins produced by some fungi from the families Clavicipitaceae, Trichocomaceae and Arthrodermataceae. Some of these compounds and their semi-synthetic derivatives are important drugs in modern medicine, such as ergotamine and dihydroergotamine, which are used for the treatment of migraines. Ergotamine , along with ergometrine, have also been used for a very long time as uterine contracting agents following childbirth.
The early part of the pathway is common to all three families and ends with chanoclavine-I aldehyde (see chanoclavine I aldehyde biosynthesis). This compound is an important branching point, and is converted to different products within the different fungal families. Within the Clavicipitaceae, such as Claviceps fusiformis, an enzyme encoded by easG converts chanoclavine-I aldehyde to agroclavine [Matuschek11], which is then converted to assorted amides and peptides of lysergate, known as ergoamides and ergopeptines, respectively. The potent synthetic hallucinogen lysergic acid diethylamide (LSD) is a diethylamide of this intermediate.
A biosynthetic gene cluster involved in ergot alkaloids biosynthesis has been identified in Claviceps purpurea. While not all steps have been associated with an enzyme, the cloA gene was shown to encode a cytochrome P-450 enzyme that catalyzes the formation of paspalate from elymoclavine, while ps1 and ps2 encode two non-ribosomal peptide synthases that form the subunits of a very large complex that catalyzes the addition of a tripeptidide tail to the lysergic moiety [Liu09].
Superpathways: superpathway of ergotamine biosynthesis
Liu09: Liu X, Wang L, Steffan N, Yin WB, Li SM (2009). "Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the acetylation of fumigaclavine B." Chembiochem 10(14);2325-8. PMID: 19672909
Matuschek11: Matuschek M, Wallwey C, Xie X, Li SM (2011). "New insights into ergot alkaloid biosynthesis in Claviceps purpurea: an agroclavine synthase EasG catalyses, via a non-enzymatic adduct with reduced glutathione, the conversion of chanoclavine-I aldehyde to agroclavine." Org Biomol Chem 9(11);4328-35. PMID: 21494745
Correia03: Correia T, Grammel N, Ortel I, Keller U, Tudzynski P (2003). "Molecular cloning and analysis of the ergopeptine assembly system in the ergot fungus Claviceps purpurea." Chem Biol 10(12);1281-92. PMID: 14700635
Haarmann06: Haarmann T, Ortel I, Tudzynski P, Keller U (2006). "Identification of the cytochrome P450 monooxygenase that bridges the clavine and ergoline alkaloid pathways." Chembiochem 7(4);645-52. PMID: 16538694
Rigbers08: Rigbers O, Li SM (2008). "Ergot alkaloid biosynthesis in Aspergillus fumigatus. Overproduction and biochemical characterization of a 4-dimethylallyltryptophan N-methyltransferase." J Biol Chem 283(40);26859-68. PMID: 18678866
Wallwey12: Wallwey C, Heddergott C, Xie X, Brakhage AA, Li SM (2012). "Genome mining reveals the presence of a conserved biosynthetic gene cluster for the biosynthesis of ergot alkaloid precursors in the fungal family Arthrodermataceae." Microbiology. PMID: 22403186
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