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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
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MetaCyc Pathway: ergotamine biosynthesis

Enzyme View:

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

Some taxa known to possess this pathway include ? : Claviceps purpurea , Epichloe festucae

Expected Taxonomic Range: Clavicipitaceae

Summary:
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.

Ergotamine is the major alkaloid produced by Claviceps purpurea and related species.

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

Credits:
Created 16-Apr-2010 by Pujar A , Boyce Thompson Institute
Revised 01-Jun-2012 by Caspi R , SRI International


References

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Clay02: Clay K, Schardl C (2002). "Evolutionary origins and ecological consequences of endophyte symbiosis with grasses." Am Nat 160 Suppl 4;S99-S127. PMID: 18707456

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Riederer96: Riederer B, Han M, Keller U (1996). "D-Lysergyl peptide synthetase from the ergot fungus Claviceps purpurea." J Biol Chem 271(44);27524-30. PMID: 8910337

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

Tudzynski99: Tudzynski P, Holter K, Correia T, Arntz C, Grammel N, Keller U (1999). "Evidence for an ergot alkaloid gene cluster in Claviceps purpurea." Mol Gen Genet 261(1);133-41. PMID: 10071219

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

Walzel97: Walzel B, Riederer B, Keller U (1997). "Mechanism of alkaloid cyclopeptide synthesis in the ergot fungus Claviceps purpurea." Chem Biol 4(3);223-30. PMID: 9115414


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, BIOCYC13B.