FRBC_BLOB1
ID FRBC_BLOB1 Reviewed; 561 AA.
AC A0A0S6XHF8;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Acyl-CoA ligase frbB {ECO:0000303|PubMed:27660098};
DE EC=6.2.1.- {ECO:0000305|PubMed:27660098};
DE AltName: Full=FR901469 biosynthesis cluster protein B {ECO:0000303|PubMed:27660098};
GN Name=frbC {ECO:0000303|PubMed:27660098}; ORFNames=ANO11243_029870;
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: Acyl-CoA ligase; 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 -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor frbF. {ECO:0000269|PubMed:27660098}.
CC -!- DOMAIN: Both substrate-binding domains (SBD1 and SBD2) are involved in
CC the substrate recognition, and are sufficient to confer the substrate
CC specificity. {ECO:0000250|UniProtKB:Q42524}.
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 ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; DF938583; GAM84984.1; -; Genomic_DNA.
DR OrthoDB; 683933at2759; -.
DR Proteomes; UP000054361; Unassembled WGS sequence.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Nucleotide-binding; Reference proteome.
FT CHAIN 1..561
FT /note="Acyl-CoA ligase frbB"
FT /id="PRO_0000454572"
FT REGION 284..354
FT /note="SBD1"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT REGION 355..417
FT /note="SBD2"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT BINDING 213..221
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 354..359
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 437
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 456
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 551
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
SQ SEQUENCE 561 AA; 61133 MW; C06ABC15FE5AE802 CRC64;
MVIFKSPLPV GQHQSLEVIA PVGELALNVH LALAKQHEVK PPFIDVMSGK AWHAEEIRDR
VDHLARVLAK QFGWQPNVGT PWDKVVAIYS YNTVDFIILS WAVHRLGGLC LLLHSTSSAG
EIAAHLKRVQ CAAIFTNEPL LATTRKAREL LNGEPQKIFI LDVANELLPE GHVNSDLTTV
EQLAQKGAEL EALEPLKWDA VNGRDQVAYL CPTSGTSGAQ KLAKVTHGGL LANAVQTVAH
ELKTNQGKTE VGLNFLPCSH IYGMMLSHTM ATRGDCMVLH PFFDLKRVLG SIARFRIERL
YLVPSIISAL TRNPFLLDMV DLSSVTSVVT GAAPFGSSLA DGLHTLRPKW HLQPGWGLTE
GGGASSLTPK DDFVPGSSGV LLPLTEVRLI GEDGKDAEGH EVRGEIYMKS PSVIAGYLED
ANTQNPFTED GWLRTGDIGM FKVSPKGVEH LWVVDRVKDM IKVKGMQVAP AELEAHLLLL
PQIAEVAVIG VADKISGERP KAFIVQAKNA GPEEQLRETI NQHVEATLSE PHWLGKRIEF
VNDLPKTSSG KAMKSVLRAK A
