A role for Old Yellow Enzyme in ergot alkaloid biosynthesis.
Ergot alkaloids, secondary metabolites produced by filamentous fungi, elicit a diverse array of pharmacological effects. The biosynthesis of this class of natural products has not been fully elucidated. Here we demonstrate that a homologue of Old Yellow Enzyme encoded in the Aspergillus fumigatus ergot gene cluster catalyzes reduction of the alpha,beta unsaturated alkene of chanoclavine-I aldehyde 3. This reduction, which yields dihydrochanoclavine aldehyde, facilitates an intramolecular reaction between a secondary amine and aldehyde to form the D ring of the ergot alkaloid structural framework.
Cheng
Johnathan Z
JZ
Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Coyle
Christine M
CM
Panaccione
Daniel G
DG
O'Connor
Sarah E
SE
D000447:Aldehydes / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000235:genetics; D055162:Biocatalysis; D001688:Biological Products / Q000096:biosynthesis; D004873:Ergolines / Q000378:metabolism; D004876:Ergot Alkaloids / Q000096:biosynthesis* / Q000378:metabolism; D005810:Multigene Family; D009252:NADPH Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D017386:Sequence Homology, Amino Acid
D000447:Aldehydes; D001688:Biological Products; D004873:Ergolines; D004876:Ergot Alkaloids; C006959:chanoclavine; D009252:NADPH Dehydrogenase