FRBH_BLOB1
ID FRBH_BLOB1 Reviewed; 321 AA.
AC A0A0S6XGJ8;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=2-oxoglutarate-dependent dioxygenase frbH {ECO:0000303|PubMed:27660098};
DE EC=1.14.-.- {ECO:0000305|PubMed:27660098};
DE AltName: Full=FR901469 biosynthesis cluster protein H {ECO:0000303|PubMed:27660098};
GN Name=frbH {ECO:0000303|PubMed:27660098}; ORFNames=ANO11243_029920;
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 -!- 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; GAM84989.1; -; 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..321
FT /note="2-oxoglutarate-dependent dioxygenase frbH"
FT /id="PRO_0000454569"
FT DOMAIN 169..273
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 77..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 194
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 196
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 251
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 264
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 321 AA; 36235 MW; A5A05984BD112498 CRC64;
MSQQEAVDAA FLPTLDLSRL VSSDAEERQK LVRACEVYGF FYLDLRSDAE LIALWTGVLD
LMGQYFNLSL DEKMRDSRNS DTHGYEPVAT STGAQDDLPD YYESLKASRD EVLTQSSKLA
PAVKANHALL NRFIERAHAV TMMILRQLSI ALELDDSHKF EAFHRHSEES LSTLSMFRYP
KQEVLDVGVG HNKHTDIGTL TFLLCQQQGL QVLSKDPVGW RFVQPLPGCA VINVGDTLRF
LSGSRFRSAV HRVIPVDQLQ RQDRFSIAYF LRAENNATLN AVGGRTVSAK DWHDEKFDVF
RKSREAQASD DVLTGGMERD M
