Q4WR21 · HELD1_ASPFU
- ProteinAcyltransferase helD1
- GenehelD1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids478 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Acyltransferase; part of the gene cluster that mediates the biosynthesis of helvolic acid, an antibacterial nortriterpenoid (PubMed:19216560, PubMed:19415934, PubMed:29158519).
Protostadienol synthase helA cyclizes (3S)-oxidosqualene to (17Z)-protosta-1720,24-dien-3-beta-ol (protostadienol) (PubMed:19216560, PubMed:19415934, PubMed:29158519).
The synthesis of protostadienol is followed by several steps of monooxygenation, dehydrogenation, and acyl transfer to yield the final helvolic acid (PubMed:19216560).
Following the cyclization to the tetracyclic protostadienol by helA, cytochrome P450 monooxygenases helB1-mediated and helB2-mediated oxidation at C-4 and C-16, acyltransferase helD2-dependent acetylation of 16-OH, oxidation of C-21 by cytochrome P450 monooxygenase helB4, and short chain dehydrogenase helC-dependent oxidative decarboxylation yield the fusidane skeleton (PubMed:29158519).
This intermediate is further modified in three additional steps mediated by the cytochrome P450 monooxygenase helB3, the acyltransferase helD1, and the 3-ketosteroid 1-dehydrogenase helE to give helvolic acid (PubMed:19216560, PubMed:19415934, PubMed:29158519).
Compared with the late stages in the biosynthesis of helvolic acid, enzymes involved in the early stage modifications act in a relatively strict order (PubMed:29158519).
The hydroxylation of C-16 by helB1 and subsequent acetylation by helD2 should occur before the helB3-mediated oxidation of C-21 (PubMed:29158519).
C-4 demethylation in fusidane-type antibiotics proceeds in an unusual manner though it is also achieved by oxidative decarboxylation (PubMed:19415934, PubMed:29158519).
The methyl group at C-4 beta position is oxidized by helB1 and subsequently removed by the short chain dehydrogenase helC (PubMed:19415934, PubMed:29158519).
Protostadienol synthase helA cyclizes (3S)-oxidosqualene to (17Z)-protosta-1720,24-dien-3-beta-ol (protostadienol) (PubMed:19216560, PubMed:19415934, PubMed:29158519).
The synthesis of protostadienol is followed by several steps of monooxygenation, dehydrogenation, and acyl transfer to yield the final helvolic acid (PubMed:19216560).
Following the cyclization to the tetracyclic protostadienol by helA, cytochrome P450 monooxygenases helB1-mediated and helB2-mediated oxidation at C-4 and C-16, acyltransferase helD2-dependent acetylation of 16-OH, oxidation of C-21 by cytochrome P450 monooxygenase helB4, and short chain dehydrogenase helC-dependent oxidative decarboxylation yield the fusidane skeleton (PubMed:29158519).
This intermediate is further modified in three additional steps mediated by the cytochrome P450 monooxygenase helB3, the acyltransferase helD1, and the 3-ketosteroid 1-dehydrogenase helE to give helvolic acid (PubMed:19216560, PubMed:19415934, PubMed:29158519).
Compared with the late stages in the biosynthesis of helvolic acid, enzymes involved in the early stage modifications act in a relatively strict order (PubMed:29158519).
The hydroxylation of C-16 by helB1 and subsequent acetylation by helD2 should occur before the helB3-mediated oxidation of C-21 (PubMed:29158519).
C-4 demethylation in fusidane-type antibiotics proceeds in an unusual manner though it is also achieved by oxidative decarboxylation (PubMed:19415934, PubMed:29158519).
The methyl group at C-4 beta position is oxidized by helB1 and subsequently removed by the short chain dehydrogenase helC (PubMed:19415934, PubMed:29158519).
Pathway
Mycotoxin biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 145 | Proton acceptor | ||||
Sequence: H | ||||||
Active site | 415 | Proton acceptor | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | acyltransferase activity, transferring groups other than amino-acyl groups | |
Biological Process | helvolic acid biosynthetic process | |
Biological Process | secondary metabolic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAcyltransferase helD1
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Fumigati
Accessions
- Primary accessionQ4WR21
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441951 | 1-478 | Acyltransferase helD1 | |||
Sequence: MESIPLSPFDLQGSFSNIPYAFFYENTQSENDFMPFDFLKGSLWASLQRFPILTGRLRARSTGHIVVEVDAGNPNQPDIRETLCDSVHWSQLKESSFAWDAWPAGVATVGPVATAAADGEIKLLNIHVMRLAQNSGVILFINIPHYVVDGVGYFAFINHWAETMRMQQQQQEQENEARSRFSFDRGIIQRYLPTERAPLDPLTASIYGQRNLLVDWLAWLSPTTLGGLLSKTAAMARGEAHLFRIPRASLDQVHKDVQPYIPASARLSDNDLLVALISKTYIQSQPQPKPPTGFLSWLRPGQGQPESHCTVRIPCDVRRHLKVRERYTGNLLLGMMVRTPLAELARPTSSETLAAAALNVRQSIERVQPGLVAAYHDLIQANPTSHMRPLAFTATRTTTSLVTTSQVRFPMYEADFGSGKPCFVCLTPVFAGSYTMAAILPTPEGREGGVYVLLTSNVEAMQGIKKNQYWNGLVEIIW |
Expression
Induction
Expression is under the control of the secondary metabolism regulator laeA (PubMed:17432932).
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length478
- Mass (Da)53,274
- Last updated2005-07-05 v1
- Checksum6D5ACF3033D29E16
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AAHF01000005 EMBL· GenBank· DDBJ | EAL89313.1 EMBL· GenBank· DDBJ | Genomic DNA |