W7L9F0 · FUM16_GIBM7
- ProteinAcyl-CoA synthetase FUM16
- GeneFUM16
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids676 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Acyl-CoA synthetase; part of the gene cluster that mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3 (FB3), and B4 (FB4), which are carcinogenic mycotoxins (PubMed:12620260).
On the basis of the chemical structures of fumonisins and precursor feeding studies, fumonisin biosynthesis is predicted to include at least five groups of biochemical reactions: synthesis of a linear polyketide with a single terminal carbonyl function and methyl groups at C-10 and C-14; condensation of the polyketide with alanine; reduction of the polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide carbons; and esterification of six-carbon tricarboxylic acids to two of the hydroxyls (PubMed:12620260).
The biosynthesis starts with the polyketide synthase FUM1-catalyzed carbon chain assembly from one molecule of acetyl CoA, eight molecules of malonyl CoA, and two molecules of methionine (PubMed:10413619).
The C-18 polyketide chain is released from the enzyme by a nucleophilic attack of a carbanion, which is derived from R-carbon of alanine by decarboxylation, on the carbonyl carbon of polyketide acyl chain (PubMed:12720383, PubMed:15137825).
This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl transferase FUM8 (PubMed:12720383, PubMed:15137825).
The resultant 3-keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-12,16-dimethylicosane by reductase FUM13 (PubMed:12720383, PubMed:15137825).
Subsequent oxidations at C-5, C-10, C-14 and C-15 followed by tricarballylic esterification of the hydroxyl groups on C-14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782, PubMed:15137825, PubMed:16489749).
The C-10 hydroxylation is performed by the cytochrome P450 monooxygenase FUM2 and occurs early in the biosynthesis (PubMed:16536629).
The C-5 hydroxylation is performed by the dioxygenase FUM3 and occurs late in the biosynthesis (PubMed:15066782, PubMed:15137825, PubMed:16536629, PubMed:20237561).
Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for the two remaining hydroxylations at positions C-14 and C-15 (PubMed:12620260).
The FUM11 tricarboxylate transporter makes a tricarboxylic acid precursor available for fumonisin biosynthesis via its export from the mitochondria (PubMed:12620260).
If the precursor is citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of citrate to form tricarballylic acid either before or after the CoA activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed esterification of CoA-activated tricarballylic acid to the C-14 and C-15 hydroxyls of the fumonisin backbone (PubMed:16489749, PubMed:17147424).
Alternatively, if the precursor is cis-aconitate, FUM7 may function to reduce the double bond (PubMed:17147424).
In this alternate proposal, feeding studies with tetradehydro-fumonisin B1 suggests that FUM7 cannot function on the tricarballylic ester and must therefore act before the FUM14-mediated esterification (PubMed:17147424).
On the basis of the chemical structures of fumonisins and precursor feeding studies, fumonisin biosynthesis is predicted to include at least five groups of biochemical reactions: synthesis of a linear polyketide with a single terminal carbonyl function and methyl groups at C-10 and C-14; condensation of the polyketide with alanine; reduction of the polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide carbons; and esterification of six-carbon tricarboxylic acids to two of the hydroxyls (PubMed:12620260).
The biosynthesis starts with the polyketide synthase FUM1-catalyzed carbon chain assembly from one molecule of acetyl CoA, eight molecules of malonyl CoA, and two molecules of methionine (PubMed:10413619).
The C-18 polyketide chain is released from the enzyme by a nucleophilic attack of a carbanion, which is derived from R-carbon of alanine by decarboxylation, on the carbonyl carbon of polyketide acyl chain (PubMed:12720383, PubMed:15137825).
This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl transferase FUM8 (PubMed:12720383, PubMed:15137825).
The resultant 3-keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-12,16-dimethylicosane by reductase FUM13 (PubMed:12720383, PubMed:15137825).
Subsequent oxidations at C-5, C-10, C-14 and C-15 followed by tricarballylic esterification of the hydroxyl groups on C-14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782, PubMed:15137825, PubMed:16489749).
The C-10 hydroxylation is performed by the cytochrome P450 monooxygenase FUM2 and occurs early in the biosynthesis (PubMed:16536629).
The C-5 hydroxylation is performed by the dioxygenase FUM3 and occurs late in the biosynthesis (PubMed:15066782, PubMed:15137825, PubMed:16536629, PubMed:20237561).
Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for the two remaining hydroxylations at positions C-14 and C-15 (PubMed:12620260).
The FUM11 tricarboxylate transporter makes a tricarboxylic acid precursor available for fumonisin biosynthesis via its export from the mitochondria (PubMed:12620260).
If the precursor is citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of citrate to form tricarballylic acid either before or after the CoA activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed esterification of CoA-activated tricarballylic acid to the C-14 and C-15 hydroxyls of the fumonisin backbone (PubMed:16489749, PubMed:17147424).
Alternatively, if the precursor is cis-aconitate, FUM7 may function to reduce the double bond (PubMed:17147424).
In this alternate proposal, feeding studies with tetradehydro-fumonisin B1 suggests that FUM7 cannot function on the tricarballylic ester and must therefore act before the FUM14-mediated esterification (PubMed:17147424).
Pathway
Mycotoxin biosynthesis.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | lipid droplet | |
Cellular Component | plasma membrane | |
Molecular Function | ATP binding | |
Molecular Function | long-chain fatty acid-CoA ligase activity | |
Biological Process | long-chain fatty-acyl-CoA metabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAcyl-CoA synthetase FUM16
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Hypocreomycetidae > Hypocreales > Nectriaceae > Fusarium > Fusarium fujikuroi species complex
Accessions
- Primary accessionW7L9F0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
Disruption phenotype
Does not affect fumonisin production (PubMed:17147424).
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441149 | 1-676 | Acyl-CoA synthetase FUM16 | |||
Sequence: MYHTVPYTIESPGYLKVAGESLPRRHPRAKHGLLRYPSAGVLTVFDIVRRSAKLYPDNKAVGSRRLIKMHREFKIIQDKEKEWIYYELGPYNYLSYSQYELLAIQIGSGLRKLGLSSSNKVYLFGTTSANWISMSHGCASQGIPIVTGYDTLSATDIQHSLSQTHAEVIYLDPHLLGTASIALENSQVKTVIINTGSIFSGGYDIDQFRNEHPQFNVITYEELIQLGRHNLKEPIPVKSSDLFCIMYTSGSTGLPNGCCITHENFLAGITGLLGGIDDFVSDQERVLAYLPLAHIFEMALENLVMYIGGTLGYGNPKTLTDASLRECNGDMVEFKPTIMVGVPQIWETIRKAVLSKLNCSGFVAKTVFWTAMSFKSFAVRYSLPGKGVFDDLVFGRVRQMTGGRLRYILNGSSGIADSTKEFLSLIVAEMLTGYGLTETCANGALSSPFEQTTSAIGSTSPAIDVKLVSIPELGYFTDADAGPCQGEILVRGPAVFKGYFNNPQGTEKAFAPGGWFKTGDIGEFDDRGHLKIIDRIKSLVKMQGGEYIALEKLESIYRTSQAILQVMVHADFEYTRPIVIIMPNTKFLQDKSRELGFSDDDSTLSSERMSAYVLDDLQDIARRSGLSKIETVTGVVITDIEWTPQSGLVTPTMKLNRRFILNYFRDEVEKCMQSIG |
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 552-655 | AMP-binding | ||||
Sequence: KLESIYRTSQAILQVMVHADFEYTRPIVIIMPNTKFLQDKSRELGFSDDDSTLSSERMSAYVLDDLQDIARRSGLSKIETVTGVVITDIEWTPQSGLVTPTMKL |
Sequence similarities
Belongs to the ATP-dependent AMP-binding enzyme family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length676
- Mass (Da)74,927
- Last updated2014-04-16 v1
- ChecksumA509BC95F7FB51B7
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
W7LL87 | W7LL87_GIBM7 | FVEG_00326 | 543 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF155773 EMBL· GenBank· DDBJ | AAN74819.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
CM000578 EMBL· GenBank· DDBJ | EWG36208.1 EMBL· GenBank· DDBJ | Genomic DNA |