A0A0S6XHH0 · FRBI_DOTX1
- ProteinFR901469 synthetase
- GenefrbI
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids15639 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of the antifungal antibiotic FR901469, an inhibitor of beta-1,3-glucansynthase, exerting antifungal activity against the pathogenes Candida albicans and Aspergillus fumigatus (PubMed:27660098).
FR901469 is a cyclic depsipeptide containing 12 amino acid residues and a fatty acid chain (PubMed:27660098).
The NRPS frbI contains 12 modules responsible for the formation of the depsipeptide backbone which is denoted as Acyl-Thr-Ala-Tyr-Val-4OHPro-Thr-Thr-3OHPro-threo3OHGln-Gly-Thr-Orn-OH (C71H116N14O23) (Probable). The PKS frbB is probably involved in the production of the hydrocarbon chain, and the acyl-CoA ligase frbC might be involved in the transport of the chain to the peptide ptoduct of frbI (Probable). Because FR901469 contains 3 hydroxylated amino acid residues, the 3 oxygenases frbA, frbH, and frbJ might be participating in amino acid hydroxylation (Probable). As no thioesterase domains were detected in frbI or frbB, the thioesterases frbD and frbE may instead release and cyclize the products of the NRPS and PKS, respectively (Probable)
FR901469 is a cyclic depsipeptide containing 12 amino acid residues and a fatty acid chain (PubMed:27660098).
The NRPS frbI contains 12 modules responsible for the formation of the depsipeptide backbone which is denoted as Acyl-Thr-Ala-Tyr-Val-4OHPro-Thr-Thr-3OHPro-threo3OHGln-Gly-Thr-Orn-OH (C71H116N14O23) (Probable). The PKS frbB is probably involved in the production of the hydrocarbon chain, and the acyl-CoA ligase frbC might be involved in the transport of the chain to the peptide ptoduct of frbI (Probable). Because FR901469 contains 3 hydroxylated amino acid residues, the 3 oxygenases frbA, frbH, and frbJ might be participating in amino acid hydroxylation (Probable). As no thioesterase domains were detected in frbI or frbB, the thioesterases frbD and frbE may instead release and cyclize the products of the NRPS and PKS, respectively (Probable)
Biotechnology
FR901469 inhibits the activity of 1,3-beta-glucan synthase from Candida albicans and Aspergillus fumigatus (PubMed:11099224, PubMed:11099225).
With minimal inhibitory concentrations (MICs) against Candida albicans and Aspergillus fumigatus of 0.63 ug/ml and 0.16 ug/ml, repectively, FR901469 displays greater inhibitory activity than other 1,3-beta-glucan synthase inhibitors such as, WF11899A, echinocandin B, aculeacin A, and papulacandin B (PubMed:11099224, PubMed:11099225).
With minimal inhibitory concentrations (MICs) against Candida albicans and Aspergillus fumigatus of 0.63 ug/ml and 0.16 ug/ml, repectively, FR901469 displays greater inhibitory activity than other 1,3-beta-glucan synthase inhibitors such as, WF11899A, echinocandin B, aculeacin A, and papulacandin B (PubMed:11099224, PubMed:11099225).
Pathway
Antifungal biosynthesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Molecular Function | ligase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | amino acid activation for nonribosomal peptide biosynthetic process | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFR901469 synthetase
- EC number
- Short namesNRPS frbI
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Dothideomycetes > Dothideomycetidae
Accessions
- Primary accessionA0A0S6XHH0
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000454567 | 1-15639 | FR901469 synthetase | ||
Modified residue | 42 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 1145 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 2691 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 4230 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 5321 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 6412 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 7507 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 9052 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 10147 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 11254 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 12335 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 13420 | O-(pantetheine 4'-phosphoryl)serine | |||
Modified residue | 14953 | O-(pantetheine 4'-phosphoryl)serine | |||
Keywords
- PTM
Expression
Induction
Expression is positively regulated by the cluster-specific transcription factor frbF.
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 5-81 | Carrier 1 | |||
Compositional bias | 82-94 | Acidic residues | |||
Region | 82-105 | Disordered | |||
Region | 140-553 | Condensation 1 | |||
Region | 579-971 | Adenylation 1 | |||
Domain | 1108-1184 | Carrier 2 | |||
Region | 1219-1626 | Epimerase 1 | |||
Region | 1667-2097 | Condensation 2 | |||
Region | 2122-2518 | Adenylation 2 | |||
Domain | 2654-2730 | Carrier 3 | |||
Region | 2761-3176 | Epimerase 2 | |||
Region | 3215-3640 | Condensation 3 | |||
Region | 3669-4059 | Adenylation 3 | |||
Domain | 4193-4269 | Carrier 4 | |||
Region | 4316-4714 | Condensation 4 | |||
Region | 4756-5149 | Adenylation 4 | |||
Domain | 5284-5360 | Carrier 5 | |||
Region | 5402-5802 | Condensation 5 | |||
Region | 5847-6238 | Adenylation 5 | |||
Domain | 6375-6451 | Carrier 6 | |||
Region | 6494-6889 | Condensation 6 | |||
Region | 6952-7335 | Adenylation 6 | |||
Domain | 7473-7546 | Carrier 7 | |||
Region | 7580-7992 | Epimerase 3 | |||
Region | 8034-8459 | Condensation 7 | |||
Region | 8486-8882 | Adenylation 7 | |||
Domain | 9015-9091 | Carrier 8 | |||
Region | 9136-9535 | Condensation 8 | |||
Region | 9583-9974 | Adenylation 8 | |||
Domain | 10110-10186 | Carrier 9 | |||
Region | 10186-10208 | Disordered | |||
Compositional bias | 10187-10206 | Acidic residues | |||
Region | 10240-10662 | Condensation 9 | |||
Region | 10683-11082 | Adenylation 9 | |||
Domain | 11217-11293 | Carrier 10 | |||
Region | 11329-11725 | Condensation 10 | |||
Region | 11770-12165 | Adenylation 10 | |||
Domain | 12298-12374 | Carrier 11 | |||
Region | 12418-12830 | Condensation 11 | |||
Region | 12861-13249 | Adenylation 11 | |||
Domain | 13383-13459 | Carrier 12 | |||
Region | 13476-13901 | Epimerase 4 | |||
Region | 13940-14369 | Condensation 12 | |||
Region | 14390-14789 | Adenylation 12 | |||
Domain | 14916-14992 | Carrier 13 | |||
Region | 15062-15433 | Condensation 13 | |||
Region | 15434-15511 | Disordered | |||
Compositional bias | 15482-15494 | Basic and acidic residues | |||
Compositional bias | 15495-15511 | Polar residues | |||
Region | 15617-15639 | Disordered | |||
Domain
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. FrbI has the following architecture: T-C-A-T-E-C-A-T-E-C-A-T-C-A-T-C-A-T-C-A-T-E-C-A-T-C-A-T-C-A-T-C-A-T-C-A-T-E-C-A-T-C.
Sequence similarities
Belongs to the NRP synthetase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length15,639
- Mass (Da)1,711,325
- Last updated2016-02-17 v1
- MD5 Checksum776A664D4F9880FFF26352A25C6EC27D
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 82-94 | Acidic residues | |||
Compositional bias | 10187-10206 | Acidic residues | |||
Compositional bias | 15482-15494 | Basic and acidic residues | |||
Compositional bias | 15495-15511 | Polar residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DF938583 EMBL· GenBank· DDBJ | GAM84991.1 EMBL· GenBank· DDBJ | Genomic DNA |