Protein: Chanoclavine-I dehydrogenase easD (ChaDH) (EC 1.1.1.332) (Ergot alkaloid synthesis protein A) (Q4WZ66)
Organism: Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293) (Neosartorya fumigata)
Function: Chanoclavine-I dehydrogenase; part of the gene cluster that mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid. DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan. The second step is catalyzed by the methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by EasD in the presence of NAD(+), resulting in the formation of chanoclavine-I aldehyde. EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form 6,8-dimethyl-6,7-didehydroergoline. EasG then catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form festuclavine. Hydrolysis of festuclavine by easM then leads to the formation of fumigaclavine B which is in turn acetylated by easN to fumigaclavine A. Finally, easL catalyzes the conversion of fumigaclavine A into fumigaclavine C by attaching a dimethylallyl moiety to C-2 of the indole nucleus.
Sequence: MASVESRIIAITGGASGIGAATCRLLAERGAAVLCVCDISPKNFDDLKISIKKINPSTKVHCATVDVTSSVEVRQWIEGIISDFGDLHGAVNAAGIAQGAGMRNTPTIAEEVDEEWTRIMNTNLNGVFYCTREEVRAMKGLPATDRSIVNVGSIASVSHMPDVYAYGTSKGACAYFTTCVAADAFPLGIRINNVSPGVTNTPMLPQFAPMAKTFEEIEESYKKEGLSLIEAEDVARTIVWLLSEDSRPVFGANINVGACMP
InterPro domains: - IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [2-257]
- IPR002347: Short-chain dehydrogenase/reductase SDR (family) [8-244]
Interaction partners: - Chanoclavine-I aldehyde reductase easA
- Tryptophan dimethylallyltransferase
- Catalase easC
- FAD-linked oxidoreductase easE
- 4-dimethylallyltryptophan N-methyltransferase easF
- Festuclavine dehydrogenase easG
- Short-chain alcohol dehydrogenase, putative
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0016614 (oxidoreductase activity, acting on CH-OH group of donors), GO:0016616 (oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0044238 (primary metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0044282 (small molecule catabolic process), GO:0044248 (cellular catabolic process), GO:0044255 (cellular lipid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006520 (amino acid metabolic process), GO:0009404 (toxin metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006629 (lipid metabolic process), GO:0006082 (organic acid metabolic process), GO:1901575 (organic substance catabolic process), GO:0006790 (sulfur compound metabolic process), GO:0044273 (sulfur compound catabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0043436 (oxoacid metabolic process), GO:1901605 (alpha-amino acid metabolic process), GO:0016042 (lipid catabolic process), GO:1901605 (alpha-amino acid metabolic process), GO:0016054 (organic acid catabolic process), GO:0006637 (acyl-CoA metabolic process), GO:0044272 (sulfur compound biosynthetic process), GO:0016053 (organic acid biosynthetic process), GO:0009063 (amino acid catabolic process), GO:1901361 (organic cyclic compound catabolic process), GO:0046395 (carboxylic acid catabolic process), GO:0046394 (carboxylic acid biosynthetic process), GO:0035834 (indole alkaloid metabolic process), GO:0019752 (carboxylic acid metabolic process), GO:0009066 (aspartate family amino acid metabolic process), GO:1901606 (alpha-amino acid catabolic process), GO:0009068 (aspartate family amino acid catabolic process), GO:0006566 (threonine metabolic process), GO:1901606 (alpha-amino acid catabolic process), GO:0072330 (monocarboxylic acid biosynthetic process), GO:0032787 (monocarboxylic acid metabolic process), GO:0046395 (carboxylic acid catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)