A0A1B4XBH0 · SDNE_SORAA
- ProteinCytochrome P450 monooxygenase sdnE
- GenesdnE
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids517 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of sordarin and hypoxysordarin, glycoside antibiotics with a unique tetracyclic diterpene aglycone structure (PubMed:27072286).
First, the geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate (PubMed:27072286).
The diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford cycloaraneosene (PubMed:27072286).
Cycloaraneosene is then hydroxylated four times by the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH to give a hydroxylated cycloaraneosene derivative such as cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286).
Although the order of the hydroxylations is unclear, at least C8, C9 and C13 of the cycloaraneosene skeleton are hydroxylated before the sordaricin formation (PubMed:27072286).
Dehydration of the 13-hydroxy group of the hydroxylated cycloaraneosene derivative might be catalyzed by an unassigned hypothetical protein such as sdnG and sdnP to construct the cyclopentadiene moiety (PubMed:27072286).
The FAD-dependent oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-Villiger oxidation to give the lactone intermediate (PubMed:27072286).
The presumed lactone intermediate would be hydrolyzed to give an acrolein moiety and a carboxylate moiety (PubMed:27072286).
Then, [4+2]cycloaddition would occur between the acrolein moiety and the cyclopentadiene moiety to give sordaricin (PubMed:27072286).
SdnN might also be involved in the [4+2]cycloaddition after the hypothesized oxidation to accommodate the oxidized product and prompt the [4+2]cycloaddition (PubMed:27072286).
GDP-6-deoxy-D-altrose may be biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-dehydratase sdnI and the short-chain dehydrogenase sdnK (PubMed:27072286).
The glycosyltransferase sdnJ catalyzes the attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin to give 4'-O-demethylsordarin (PubMed:27072286).
The methyltransferase sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would be constructed by an iterative type I PKS sdnO and the trans-acting polyketide methyltransferase sdnL. SdnL would be responsible for the introduction of an alpha-methyl group of the polyketide chain (PubMed:27072286).
Alternatively, the beta-lactamase-like protein sdnR might be responsible for the cleavage and transfer of the polyketide chain from the PKS sdnO to sordarin (PubMed:27072286).
Two putative cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the epoxidations of the polyketide chain to complete the biosynthesis of hypoxysordarin (PubMed:27072286).
Transcriptional regulators sdnM and sdnS are presumably encoded for the transcriptional regulation of the expression of the sdn gene cluster (PubMed:27072286).
First, the geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate (PubMed:27072286).
The diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford cycloaraneosene (PubMed:27072286).
Cycloaraneosene is then hydroxylated four times by the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH to give a hydroxylated cycloaraneosene derivative such as cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286).
Although the order of the hydroxylations is unclear, at least C8, C9 and C13 of the cycloaraneosene skeleton are hydroxylated before the sordaricin formation (PubMed:27072286).
Dehydration of the 13-hydroxy group of the hydroxylated cycloaraneosene derivative might be catalyzed by an unassigned hypothetical protein such as sdnG and sdnP to construct the cyclopentadiene moiety (PubMed:27072286).
The FAD-dependent oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-Villiger oxidation to give the lactone intermediate (PubMed:27072286).
The presumed lactone intermediate would be hydrolyzed to give an acrolein moiety and a carboxylate moiety (PubMed:27072286).
Then, [4+2]cycloaddition would occur between the acrolein moiety and the cyclopentadiene moiety to give sordaricin (PubMed:27072286).
SdnN might also be involved in the [4+2]cycloaddition after the hypothesized oxidation to accommodate the oxidized product and prompt the [4+2]cycloaddition (PubMed:27072286).
GDP-6-deoxy-D-altrose may be biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-dehydratase sdnI and the short-chain dehydrogenase sdnK (PubMed:27072286).
The glycosyltransferase sdnJ catalyzes the attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin to give 4'-O-demethylsordarin (PubMed:27072286).
The methyltransferase sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would be constructed by an iterative type I PKS sdnO and the trans-acting polyketide methyltransferase sdnL. SdnL would be responsible for the introduction of an alpha-methyl group of the polyketide chain (PubMed:27072286).
Alternatively, the beta-lactamase-like protein sdnR might be responsible for the cleavage and transfer of the polyketide chain from the PKS sdnO to sordarin (PubMed:27072286).
Two putative cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the epoxidations of the polyketide chain to complete the biosynthesis of hypoxysordarin (PubMed:27072286).
Transcriptional regulators sdnM and sdnS are presumably encoded for the transcriptional regulation of the expression of the sdn gene cluster (PubMed:27072286).
Cofactor
Pathway
Antibiotic biosynthesis.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | monooxygenase activity | |
Molecular Function | oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | |
Biological Process | antibiotic biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 monooxygenase sdnE
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Sordariomycetidae > Sordariales > Sordariaceae > Sordaria
Accessions
- Primary accessionA0A1B4XBH0
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 4-24 | Helical | ||||
Sequence: SSILQTLAVLYVLYLLGLIIY | ||||||
Transmembrane | 219-239 | Helical | ||||
Sequence: FPVVFIILGLSPRAMLKLVVP |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441050 | 1-517 | Cytochrome P450 monooxygenase sdnE | |||
Sequence: MMDSSILQTLAVLYVLYLLGLIIYRLYFSPLAKFPGPKLAACSKWYEFYYDVILRGQFTFQIQRMHQKYGPIVRINPFELHIQDSTFWDELYTKNKEYERYAWMSGRFGANTTTSSTVKSDLHATRRAPLNPMFSKRSITEFEPIVHEKVGLLSKRLAEYAKNGEVLEMNSAFNAFAGDVISSYCFGFSFDQLKSSGFKDNFHAAYEAVRKFAHFGLQFPVVFIILGLSPRAMLKLVVPNIYKMFVLQKDLQSKISAIIQDHQGNPEDIDSKSSLNTHSHPTIFDELLRSKLPPSEKTVRRLGSEAQQMIGAGVETVAWALTTTVFYLLSDHACLDKLRAELKAAIPDPANLPSSTALEKLPYLSACVKEGIRLSTGVSVRLPRVSPHKPIVYGGWVIPPIVPVSMTTLDVLRDPEVFTSPNNFIPERWLGSPKVANTGESLAKYFVPFGKGPRMCIGINLAYVEMHLTLAMLFRRFTFELYETDVSDVEIKHDFMVPQPKLSTKGVRAKVTGLVVE | ||||||
Glycosylation | 111 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
PTM databases
Structure
Sequence
- Sequence statusComplete
- Length517
- Mass (Da)58,384
- Last updated2016-11-02 v1
- Checksum0BD9A28693B91532