Protein: Flavin-dependent halogenase otaD (A2R6G7)
Organism: Aspergillus niger (strain ATCC MYA-4892 / CBS 513.88 / FGSC A1513)
Function: Flavin-dependent halogenase; part of the gene cluster that mediates the biosynthesis of ochratoxin A (OTA), a mycotoxin composed of a chlorinated type I polyketide dihydroisocoumarin moiety linked to L-phenylalanine, and demonstrated to have nephrotoxic, immunotoxic, genotoxic, neurotoxic, and teratogenic properties. OtaD chlorinates ochratoxin B (OTB) at the C-5 position to form OTA (By similarity). The pathway begins with the highly reducing polyketide synthase otaA that catalyzes the formation of the isocoumarin group during the initial stages of biosynthesis, starting from one acetate and 4 malonate units, to originate the characteristic pentaketide skeleton 7-methylmellein (7-MM) of the OTA molecule. The newly identified cyclase otaY might be involved in the polyketide cyclization reaction during the initial steps of the OTA biosynthesis. 7-MM is then oxidized into 7-carboxymellein (also called ochratoxin beta) by the cytochrome P450 monooxygenase otaC. The NRPS encoded by the otaB gene is involved in the linking of phenylalanine to the dihydroisocoumarin ring. The reaction catalyzed by NRPS results in the production of ochratoxin B (OTB), which is the non-chlorinated analog of OTA and which subsequently serves as the substrate of the halogenase otaD for chlorination activity to form the final molecular structure of OTA, containing a chlorine atom in the C-5 position of the molecule (Probable)
Sequence: MEIPHKATVLVIGGGPGGSYTASALAREGIDIVLLEADVFPRFIDLDETFVNYGFVRKNASHGSLADTDFILQPGADTFAWNVVRSECDDLMFKHASNSGARAFDGVKVTAIEFDPLDESAIDDHPGRPVSASWKAKDGRTGSISFDYLVDASGRAGIASTKYLKSRTYNSYLKNVASWGYWRGATPYGVGTSVEGQPYFEALQDGSGWVWFIPLHNGTTSVGVVMNQELATQKKKSSTVTSSRAFYLESVEGARVISQLLQPANLDGEIKQASDWSYNASSYGSPYLRIVGDAGAFIDPYFSSGVHLAVSGGLSAAVSIAASIRGDCPEHTAWQWHSQGVANRYGRFLLVVLGATKQIRARDSPVLNSEGQDGFDDAFAVIRPVIQGTADVQGKVSAREVLDAVTFSTNAVRPSAGGQNVVLEESSRSLRSQVEQEMGDVANSLAKAYKDTDVYEGLMARLERGSLGLKAVGVMG
InterPro domains: - IPR036188: FAD/NAD(P)-binding domain superfamily (homologous_superfamily) [5-406]
- IPR050816: Flavin-dependent Halogenases in Natural Product Biosynthesis (family) [1-398]
- IPR002938: FAD-binding domain (domain) [7-37]
- IPR006905: Flavin-dependent halogenase (family) [133-313]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0016705 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0006575 (cellular modified amino acid metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:0006082 (organic acid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043603 (amide metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0042398 (cellular modified amino acid biosynthetic process), GO:0016053 (organic acid biosynthetic process), GO:0043436 (oxoacid metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:0043604 (amide biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0019752 (carboxylic acid metabolic process), GO:0046394 (carboxylic acid biosynthetic process), GO:0072330 (monocarboxylic acid biosynthetic process), GO:0032787 (monocarboxylic acid metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0042579 (microbody), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005777 (peroxisome)