Q6UEH5 · AFLF_ASPPU
- ProteinNorsolorinic acid reductase B
- GeneaflF
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids382 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Norsolorinic acid reductase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:15006741, PubMed:15094053).
The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741).
Within the aflatoxin pathway, the norsolorinic acid reductase aflE may play a role in the conversion of norsolorinic acid (NOR) to averantin (AVN) (PubMed:15006741).
The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. The second step is the conversion of NOR to averantin and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741).
The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741).
Within the aflatoxin pathway, the norsolorinic acid reductase aflE may play a role in the conversion of norsolorinic acid (NOR) to averantin (AVN) (PubMed:15006741).
The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. The second step is the conversion of NOR to averantin and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741).
Pathway
Mycotoxin biosynthesis; aflatoxin biosynthesis.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 64 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 69 | Proton donor | ||||
Sequence: Y | ||||||
Site | 96 | Lowers pKa of active site Tyr | ||||
Sequence: K | ||||||
Binding site | 143 | substrate | ||||
Sequence: H | ||||||
Binding site | 173-174 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SD | ||||||
Binding site | 199 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 228-238 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GVLNQGRFRTE | ||||||
Binding site | 302-310 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: RKVDHLTGV |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | oxidoreductase activity | |
Biological Process | aflatoxin biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNorsolorinic acid reductase B
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Circumdati
Accessions
- Primary accessionQ6UEH5
- Secondary accessions
Proteomes
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000424160 | 1-382 | Norsolorinic acid reductase B | |||
Sequence: MSTSAPLLSRYRQLSPAASIRVSPLCLGAMTFGVSDGEMFGECSKEMAFAILDHFYQQGGNFIDTANGYRAGESEMWLGEWMASRKNRDDIVLATKYAAGYRGHEKNRIQVNYGGTGTKSMRLSVDASLQKLQTSYIDLLYVHWWDYTVSIPELMHALNDLVASGKVHYLGISDSPAWVVSKANQYARDHGLRQFVVYQGLWNAAKRDLERDILPMCLDEGMGLCPYGVLNQGRFRTEEGFRDRDQTNNAGGRNIIPLSEHDRSVSRVLDIVATSKGVPLLQVALAYVMQKAPYVFPIVGVRKVDHLTGVEPAVHISLTDEEVNAIENAYEFDPGFPHTFLSGSMFAQGPPKGGYSPDVVWWTKMLGTFDWVEGAKPIRPQP |
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Sequence similarities
Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.
Family and domain databases
Sequence
- Sequence statusComplete
- Length382
- Mass (Da)42,555
- Last updated2004-07-05 v1
- ChecksumB3A915E8A9080605
Keywords
- Technical term