FRBA_BLOB1
ID FRBA_BLOB1 Reviewed; 337 AA.
AC A0A0S6XAW4;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=2-oxoglutarate-dependent dioxygenase frbA {ECO:0000303|PubMed:27660098};
DE EC=1.14.-.- {ECO:0000305|PubMed:27660098};
DE AltName: Full=FR901469 biosynthesis cluster protein A {ECO:0000303|PubMed:27660098};
GN Name=frbA {ECO:0000303|PubMed:27660098}; ORFNames=ANO11243_029850;
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, INDUCTION, 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: 2-oxoglutarate-dependent dioxygenase; part of the gene
CC cluster that mediates the biosynthesis of the antifungal antibiotic
CC FR901469, an inhibitor of beta-1,3-glucansynthase, exerting antifungal
CC activity against the pathogenes Candida albicans and Aspergillus
CC fumigatus (PubMed:27660098). FR901469 is a cyclic depsipeptide
CC containing 12 amino acid residues and a fatty acid chain
CC (PubMed:27660098). The NRPS frbI contains 12 modules responsible for
CC the formation of the depsipeptide backbone which is denoted as Acyl-
CC Thr-Ala-Tyr-Val-4OHPro-Thr-Thr-3OHPro-threo3OHGln-Gly-Thr-Orn-OH
CC (C71H116N14O23) (Probable). The PKS frbB is probably involved in the
CC production of the hydrocarbon chain, and the acyl-CoA ligase frbC might
CC be involved in the transport of the chain to the peptide ptoduct of
CC frbI (Probable). Because FR901469 contains 3 hydroxylated amino acid
CC residues, the 3 oxygenases frbA, frbH, and frbJ might be participating
CC in amino acid hydroxylation (Probable). As no thioesterase domains were
CC detected in frbI or frbB, the thioesterases frbD and frbE may instead
CC release and cyclize the products of the NRPS and PKS, respectively
CC (Probable). {ECO:0000269|PubMed:27660098, ECO:0000305|PubMed:27660098}.
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- PATHWAY: Antifungal biosynthesis. {ECO:0000305|PubMed:27660098}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor frbF. {ECO:0000269|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 iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; DF938583; GAM84982.1; -; Genomic_DNA.
DR OrthoDB; 622449at2759; -.
DR Proteomes; UP000054361; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..337
FT /note="2-oxoglutarate-dependent dioxygenase frbA"
FT /id="PRO_0000454568"
FT DOMAIN 175..290
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 202
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 204
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 262
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 281
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 337 AA; 37730 MW; F695F772FC4B4E50 CRC64;
MSIPSLDYRL FSHGDPAQRQ QFCEDLVKTF AGYGFAKLRN HGLSDERVDE AFSYSNKFFN
LPLHIKQKAK HPEAPNPHRG YSGVGQEKIS AITGFEKGER SEVRAAELRE SWDQGPADDE
LYANRWMPDE DLPGYRSFME SFFVECQTLH QSLLQCIATG LSLPSDELSS RCAKCSAELR
LNHYPATPAS SLASGACRIS PHSDFGTITL LFQDSVGGLQ VEDQQNPGVF LPVEPDDVHE
MIINVGDCLS RWTDGRLRSV NHRVVSPTRL PGDADVMIPE RHSLAYFGKP SRDEVVDSLP
LFVPEGCKPK FADRWTALEY NQSKLMRTYN VETAAQG
