Detail Information for IndEnz0010000179
IED ID IndEnz0010000179
Enzyme Type ID esterase000179
Protein Name 5'-hydroxyaverantin dehydrogenase
HAVN dehydrogenase
EC 1.1.1.352
Dothistromin biosynthesis protein adhA
Gene Name adhA DOTSEDRAFT_48495
Organism Dothistroma septosporum (strain NZE10 / CBS 128990) (Red band needle blight fungus) (Mycosphaerella pini)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta dothideomyceta Dothideomycetes Dothideomycetidae Mycosphaerellales Mycosphaerellaceae Dothistroma Dothistroma septosporum (Red band needle blight fungus) (Mycosphaerella pini) Dothistroma septosporum (strain NZE10 / CBS 128990) (Red band needle blight fungus) (Mycosphaerella pini)
Enzyme Sequence MEALNTNVDLAGLEGRSVLVTGGASGIGLATAKAWAAAGAYVTLADIQPIEKGEKIASDLSHNGQHVNYTFCDVTSWESQLEAFRSAVKFSPRQTLDIVATFAGTAFAPGNEVDHVLFAGEPSLDAELPAPNTKNIEVNLTGVYYSSWLALYFFRLKPSDSSEPGDKSLILVSSIGGYMDSPKASTYPASKFGVRGLFRSTRARTIDIGVRCNLLAPWFVDTPLIAPVKNAMKARGIEMSKVLAFATMEDCVQAASFCAVNKELHGRALAIQPEGTFDLKDDVEDGWAGDQLRPIMKRRREAGFDA
Enzyme Length 306
Uniprot Accession Number M2YJK1
Absorption
Active Site ACT_SITE 187; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU10001
Activity Regulation
Binding Site BINDING 191; /note=NADP; /evidence=ECO:0000250|UniProtKB:P16544
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=(1'S,5'S)-5'-hydroxyaverantin + NAD(+) = (S)-5'-oxoaverantin + H(+) + NADH; Xref=Rhea:RHEA:35475, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:77900, ChEBI:CHEBI:77933; EC=1.1.1.352; Evidence={ECO:0000250|UniProtKB:P87017}; CATALYTIC ACTIVITY: Reaction=(1'S,5'R)-5'-hydroxyaverantin + NAD(+) = (S)-5'-oxoaverantin + 2 H(+) + NADH; Xref=Rhea:RHEA:35479, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:71536, ChEBI:CHEBI:77933; EC=1.1.1.352; Evidence={ECO:0000250|UniProtKB:P87017};
DNA Binding
EC Number 1.1.1.352
Enzyme Function FUNCTION: 5'-hydroxyaverantin dehydrogenase; part of the fragmented gene cluster that mediates the biosynthesis of dothistromin (DOTH), a polyketide toxin very similar in structure to the aflatoxin precursor, versicolorin B (PubMed:12039746, PubMed:17683963, PubMed:22069571, PubMed:23207690, PubMed:23448391). The first step of the pathway is the conversion of acetate to norsolorinic acid (NOR) and requires the fatty acid synthase subunits hexA and hexB, as well as the polyketide synthase pksA (PubMed:16649078, PubMed:23207690). PksA combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor NOR (By similarity). The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase hexA/hexB (By similarity). The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase nor1, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin (PubMed:23207690). The cytochrome P450 monooxygenase avnA then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN) (PubMed:23207690). The next step is performed by adhA that transforms HAVN to averufin (AVF) (PubMed:23207690). Averufin might then be converted to hydroxyversicolorone by cypX and avfA (PubMed:23207690). Hydroxyversicolorone is further converted versiconal hemiacetal acetate (VHA) by moxY (PubMed:23207690). VHA is then the substrate for the versiconal hemiacetal acetate esterase est1 to yield versiconal (VAL) (PubMed:23207690). Versicolorin B synthase vbsA then converts VAL to versicolorin B (VERB) by closing the bisfuran ring (PubMed:16649078, PubMed:23207690). Then, the activity of the versicolorin B desaturase verB leads to versicolorin A (VERA) (PubMed:23207690). DotB, a predicted chloroperoxidase, may perform epoxidation of the A-ring of VERA (PubMed:23207690). Alternatively, a cytochrome P450, such as cypX or avnA could catalyze this step (PubMed:23207690). It is also possible that another, uncharacterized, cytochrome P450 enzyme is responsible for this step (PubMed:23207690). Opening of the epoxide could potentially be achieved by the epoxide hydrolase epoA (PubMed:23207690). However, epoA seems not to be required for DOTH biosynthesis, but other epoxide hydrolases may have the ability to complement this hydrolysis (PubMed:23207690). Alternatively, opening of the epoxide ring could be achieved non-enzymatically (PubMed:23207690). The next step is the deoxygenation of ring A to yield the 5,8-dihydroxyanthraquinone which is most likely catalyzed by the NADPH dehydrogenase encoded by ver1 (PubMed:23207690). The last stages of DOTH biosynthesis are proposed to involve hydroxylation of the bisfuran (PubMed:23207690). OrdB and norB might have oxidative roles here (PubMed:23207690). An alternative possibility is that cytochrome P450 monoogenases such as avnA and cypX might perform these steps in addition to previously proposed steps (PubMed:23207690). {ECO:0000250|UniProtKB:P87017, ECO:0000269|PubMed:12039746, ECO:0000269|PubMed:16649078, ECO:0000303|PubMed:22069571, ECO:0000305|PubMed:17683963, ECO:0000305|PubMed:23207690, ECO:0000305|PubMed:23448391}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571, ECO:0000305|PubMed:23207690}.
nucleotide Binding NP_BIND 20..48; /note=NADP; /evidence=ECO:0000250|UniProtKB:P16544
Features Active site (1); Binding site (1); Chain (1); Nucleotide binding (1)
Keywords Cytoplasm;NAD;NADP;Oxidoreductase;Reference proteome
Interact With
Induction INDUCTION: Expression is positively regulated by the dothistromin-specific transcription factors aflR and aflJ (PubMed:23207690, PubMed:25986547). {ECO:0000269|PubMed:23207690, ECO:0000269|PubMed:25986547}.
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P87017}.
Modified Residue
Post Translational Modification
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID -
Motif
Gene Encoded By
Mass 32,944
Kinetics
Metal Binding
Rhea ID RHEA:35475; RHEA:35479
Cross Reference Brenda