ID   FRBD_BLOB1              Reviewed;         261 AA.
AC   A0A0S6XGG4;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   17-FEB-2016, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Thioesterase frbD {ECO:0000303|PubMed:27660098};
DE            EC=3.1.-.- {ECO:0000305|PubMed:27660098};
DE   AltName: Full=FR901469 biosynthesis cluster protein D {ECO:0000303|PubMed:27660098};
GN   Name=frbD {ECO:0000303|PubMed:27660098}; ORFNames=ANO11243_029880;
OS   Fungal sp. (strain No.11243).
OC   Eukaryota; Fungi.
OX   NCBI_TaxID=1603295;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=25838475; DOI=10.1128/genomea.00118-15;
RA   Matsui M., Yokoyama T., Nemoto K., Kumagai T., Terai G., Arita M.,
RA   Machida M., Shibata T.;
RT   "Genome sequence of fungal species No.11243, which produces the antifungal
RT   antibiotic FR901469.";
RL   Genome Announc. 3:0-0(2015).
RN   [2]
RP   BIOTECHNOLOGY.
RX   PubMed=11099224; DOI=10.7164/antibiotics.53.912;
RA   Fujie A., Iwamoto T., Muramatsu H., Okudaira T., Nitta K., Nakanishi T.,
RA   Sakamoto K., Hori Y., Hino M., Hashimoto S., Okuhara M.;
RT   "FR901469, a novel antifungal antibiotic from an unidentified fungus
RT   No.11243. I. Taxonomy, fermentation, isolation, physico-chemical properties
RT   and biological properties.";
RL   J. Antibiot. 53:912-919(2000).
RN   [3]
RP   BIOTECHNOLOGY.
RX   PubMed=11099225; DOI=10.7164/antibiotics.53.920;
RA   Fujie A., Iwamoto T., Muramatsu H., Okudaira T., Sato I., Furuta T.,
RA   Tsurumi Y., Hori Y., Hino M., Hashimoto S., Okuhara M.;
RT   "FR901469, a novel antifungal antibiotic from an unidentified fungus
RT   No.11243. II. In vitro and in vivo activities.";
RL   J. Antibiot. 53:920-927(2000).
RN   [4]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=27660098; DOI=10.1016/j.jbiosc.2016.08.007;
RA   Matsui M., Yokoyama T., Nemoto K., Kumagai T., Terai G., Tamano K.,
RA   Machida M., Shibata T.;
RT   "Identification of a putative FR901469 biosynthesis gene cluster in fungal
RT   sp. No. 11243 and enhancement of the productivity by overexpressing the
RT   transcription factor gene frbF.";
RL   J. Biosci. Bioeng. 123:147-153(2017).
CC   -!- FUNCTION: Thioesterase; part of the gene cluster that mediates the
CC       biosynthesis of the antifungal antibiotic FR901469, an inhibitor of
CC       beta-1,3-glucansynthase, exerting antifungal activity against the
CC       pathogenes Candida albicans and Aspergillus fumigatus
CC       (PubMed:27660098). FR901469 is a cyclic depsipeptide containing 12
CC       amino acid residues and a fatty acid chain (PubMed:27660098). The NRPS
CC       frbI contains 12 modules responsible for the formation of the
CC       depsipeptide backbone which is denoted as Acyl-Thr-Ala-Tyr-Val-4OHPro-
CC       Thr-Thr-3OHPro-threo3OHGln-Gly-Thr-Orn-OH (C71H116N14O23) (Probable).
CC       The PKS frbB is probably involved in the production of the hydrocarbon
CC       chain, and the acyl-CoA ligase frbC might be involved in the transport
CC       of the chain to the peptide ptoduct of frbI (Probable). Because
CC       FR901469 contains 3 hydroxylated amino acid residues, the 3 oxygenases
CC       frbA, frbH, and frbJ might be participating in amino acid hydroxylation
CC       (Probable). As no thioesterase domains were detected in frbI or frbB,
CC       the thioesterases frbD and frbE may instead release and cyclize the
CC       products of the NRPS and PKS, respectively (Probable).
CC       {ECO:0000269|PubMed:27660098, ECO:0000305|PubMed:27660098}.
CC   -!- PATHWAY: Antifungal biosynthesis. {ECO:0000305|PubMed:27660098}.
CC   -!- BIOTECHNOLOGY: FR901469 inhibits the activity of 1,3-beta-glucan
CC       synthase from Candida albicans and Aspergillus fumigatus
CC       (PubMed:11099224, PubMed:11099225). With minimal inhibitory
CC       concentrations (MICs) against Candida albicans and Aspergillus
CC       fumigatus of 0.63 ug/ml and 0.16 ug/ml, repectively, FR901469 displays
CC       greater inhibitory activity than other 1,3-beta-glucan synthase
CC       inhibitors such as, WF11899A, echinocandin B, aculeacin A, and
CC       papulacandin B (PubMed:11099224, PubMed:11099225).
CC       {ECO:0000269|PubMed:11099224, ECO:0000269|PubMed:11099225}.
CC   -!- SIMILARITY: Belongs to the AMT4 thioesterase family. {ECO:0000305}.
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DR   EMBL; DF938583; GAM84985.1; -; Genomic_DNA.
DR   OrthoDB; 1387198at2759; -.
DR   Proteomes; UP000054361; Unassembled WGS sequence.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR001031; Thioesterase.
DR   Pfam; PF00975; Thioesterase; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   1: Evidence at protein level;
KW   Hydrolase; Reference proteome.
FT   CHAIN           1..261
FT                   /note="Thioesterase frbD"
FT                   /id="PRO_0000454573"
SQ   SEQUENCE   261 AA;  28156 MW;  2207395FC99962FA CRC64;
     MTDSPAPRAS VQLIQTGGAA MPLVLIHDAC GTIYTYHALS KLGRTVYGIG NPRFEKCTSW
     TGGIGEMAAC YHAAIKQRIR RGKILVGGWS LGGVIALEIA RLFADDAAIH VHGVVLIDSP
     FPSKATVTGE DLQLPPLPPG LPANRRQSVA FAMREAVDLL GDWDPKASWQ RADKKPPPAA
     LIRALDYLPG SSADAQRDEF LVDRMRTQKL LGWENSGLDF IRATYEAPGH HWGIFSSENV
     ACLSDTLSKA CAELEVVDGG R