A0A0S6XHH0 · FRBI_DOTX1

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)

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).

Pathway

Antifungal biosynthesis.

GO annotations

AspectTerm
Cellular Componentcytoplasm
Molecular Functionligase activity
Molecular Functionphosphopantetheine binding
Biological Processamino acid activation for nonribosomal peptide biosynthetic process
Biological Processsecondary metabolite biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    FR901469 synthetase
  • EC number
  • Short names
    NRPS frbI
  • Alternative names
    • FR901469 biosynthesis cluster protein I
    • Nonribosomal peptide synthetase frbI

Gene names

    • Name
      frbI
    • ORF names
      ANO11243_029940

Organism names

Accessions

  • Primary accession
    A0A0S6XHH0

Proteomes

Subcellular Location

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, modified residue.

Type
IDPosition(s)Description
ChainPRO_00004545671-15639FR901469 synthetase
Modified residue42O-(pantetheine 4'-phosphoryl)serine
Modified residue1145O-(pantetheine 4'-phosphoryl)serine
Modified residue2691O-(pantetheine 4'-phosphoryl)serine
Modified residue4230O-(pantetheine 4'-phosphoryl)serine
Modified residue5321O-(pantetheine 4'-phosphoryl)serine
Modified residue6412O-(pantetheine 4'-phosphoryl)serine
Modified residue7507O-(pantetheine 4'-phosphoryl)serine
Modified residue9052O-(pantetheine 4'-phosphoryl)serine
Modified residue10147O-(pantetheine 4'-phosphoryl)serine
Modified residue11254O-(pantetheine 4'-phosphoryl)serine
Modified residue12335O-(pantetheine 4'-phosphoryl)serine
Modified residue13420O-(pantetheine 4'-phosphoryl)serine
Modified residue14953O-(pantetheine 4'-phosphoryl)serine

Keywords

Expression

Induction

Expression is positively regulated by the cluster-specific transcription factor frbF.

Interaction

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain, compositional bias, region.

Type
IDPosition(s)Description
Domain5-81Carrier 1
Compositional bias82-94Acidic residues
Region82-105Disordered
Region140-553Condensation 1
Region579-971Adenylation 1
Domain1108-1184Carrier 2
Region1219-1626Epimerase 1
Region1667-2097Condensation 2
Region2122-2518Adenylation 2
Domain2654-2730Carrier 3
Region2761-3176Epimerase 2
Region3215-3640Condensation 3
Region3669-4059Adenylation 3
Domain4193-4269Carrier 4
Region4316-4714Condensation 4
Region4756-5149Adenylation 4
Domain5284-5360Carrier 5
Region5402-5802Condensation 5
Region5847-6238Adenylation 5
Domain6375-6451Carrier 6
Region6494-6889Condensation 6
Region6952-7335Adenylation 6
Domain7473-7546Carrier 7
Region7580-7992Epimerase 3
Region8034-8459Condensation 7
Region8486-8882Adenylation 7
Domain9015-9091Carrier 8
Region9136-9535Condensation 8
Region9583-9974Adenylation 8
Domain10110-10186Carrier 9
Region10186-10208Disordered
Compositional bias10187-10206Acidic residues
Region10240-10662Condensation 9
Region10683-11082Adenylation 9
Domain11217-11293Carrier 10
Region11329-11725Condensation 10
Region11770-12165Adenylation 10
Domain12298-12374Carrier 11
Region12418-12830Condensation 11
Region12861-13249Adenylation 11
Domain13383-13459Carrier 12
Region13476-13901Epimerase 4
Region13940-14369Condensation 12
Region14390-14789Adenylation 12
Domain14916-14992Carrier 13
Region15062-15433Condensation 13
Region15434-15511Disordered
Compositional bias15482-15494Basic and acidic residues
Compositional bias15495-15511Polar residues
Region15617-15639Disordered

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 status
    Complete
  • Length
    15,639
  • Mass (Da)
    1,711,325
  • Last updated
    2016-02-17 v1
  • MD5 Checksum
    776A664D4F9880FFF26352A25C6EC27D

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias82-94Acidic residues
Compositional bias10187-10206Acidic residues
Compositional bias15482-15494Basic and acidic residues
Compositional bias15495-15511Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DF938583
EMBL· GenBank· DDBJ
GAM84991.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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