FRBB_BLOB1
ID FRBB_BLOB1 Reviewed; 2625 AA.
AC A0A0S6XH49;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Highly reducing polyketide synthase frbB {ECO:0000303|PubMed:27660098};
DE Short=HR-PKS frbB {ECO:0000303|PubMed:27660098};
DE EC=2.3.1.- {ECO:0000305|PubMed:27660098};
DE AltName: Full=FR901469 biosynthesis cluster protein B {ECO:0000303|PubMed:27660098};
GN Name=frbB {ECO:0000303|PubMed:27660098}; ORFNames=ANO11243_029860;
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: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the antifungal antibiotic FR901469,
CC an inhibitor of beta-1,3-glucansynthase, exerting antifungal activity
CC against the 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: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {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}.
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DR EMBL; DF938583; GAM84983.1; -; Genomic_DNA.
DR STRING; 1603295.A0A0S6XH49; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000054361; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2625
FT /note="Highly reducing polyketide synthase frbB"
FT /id="PRO_0000454571"
FT DOMAIN 2542..2619
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 30..452
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 563..883
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 942..1252
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1490..1673
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 1907..2220
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2261..2439
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 200
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2579
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2625 AA; 286609 MW; 38D289BA42FFEFB3 CRC64;
MRNIDEHMSE RATLQSSGGY GERDSGVEPI AIIGMSCRLP GEASDPKGLW ELLASGKSAW
SKVPKDRFNM DAFHDPSNPT AGTTNTAGGH FIEEDLAAFD ADFFGMNPVE LEALDPQQRL
LMEIAYESFE NAGLPMKQLW GSNTGVYVGQ WSNDYDQNLA RDTEFPALYH TIGAGPAISS
NRLSYFFNLR GPSFTVDTGC SASLVALHSA VQSLRAGETD ASFVGGVNLL LDPQRFSYQS
KLKMFSAQGR SYSFDHRANG YGRGEGCCGL VLKRLSAAKR DGDPIRAVIR NSVLNQDGRT
PGISVPSGLA QEQAIKAAYS GARLHDGPDF VEAHGTGTAV GDPIEVKAIA AAFATIKTRD
GQPIPVGSVK GNVGHTESCA GLAGVIKAVL MLENQTIPPQ ANFERLNPSL LLDEWNLYVP
TVLEQRELRR ISVNSFGYGG TNAHVILDRA DAPTDQKRDS IFLGLDSAPQ PKRKRLLILS
ATSEEGCSKV AQSLVDYVDQ RFDSAATEAW LDRLAYTVNR KSIHSHRTTI LASDLEEMLH
QLSRVVQVPT PARVDVKSPK VAYVFSGQGA QYYNMGRELI NTWPVFTKSL QRANQQLNTL
GCEWDLMAEL SRDAESSNLD NPAFGQPAST AIQLALCDTL ADLGVVPVSV AGHSSGEIAA
AYAAHALSFE NAMTVSYHRG RLTAALVSKQ TSPAGAMLAV GTSPDVAQEY IDSIDGPSSR
VTIACYNSPS SVTLSGDIEG IEKLQQMFEN KKIFNRLLRT NGAAYHSHHM QQIEEEYRNA
LEGVEATTAK IPLISSVTGR DSGSEVFGRD YWVENLVSPV RFDEATAQLC QDISLILELG
AHETLGGPIR QTLKTLGPDA RDVRYLSCLK RKSDAASTLL TTIGEVFADG IHVDLHTANN
GFDKKLPRPL SDLPRYPFDH SRRYWHESRV SKEYKHRKFL PHELLGNMST DVNHLEPKWR
RYLKLKEIPW LRNHVVQGQI VFPAAGYLSM ALEAVRRYTL SADPEAKISS YAYRNISFGK
ALVLSDEKLD NEITLSLIPE SRTAKESWHD WVEFRIHTVS AGKPWTEHCR GRIRAVLDDS
NEDHIEATAD KRVVEQALSQ SVRFVSPSAF YNLSRQNGLD WHKPFDNLVK IRASRETSVT
VTESPRLERD DSLHNDSPYV IHPGTLDTAL FHCVCAIVYS QKKIDVPVVP SFISELVIAG
NARHAPGTRL VSHAIEVDNG EAHDVVINSA VDGHDQFLIR ARGMILAKLP GGTSRSGSRK
LTHESTWVPY CQKLTTQHLD RICKKDLPDG SAVEQNDMLN SLTVAFCRAA IEKVSYEQVR
EGYQQHFYRW MKKIVDGSML ESTPEPFMNG HLTNGLTNGI TSNGTKHIPN GLSNGISKHQ
VNGIANGLPQ DASNHIAQKH PDASSLTPKE NALKVLTNGL SKDLPNGVSG KHDEFEILKS
SSASPGEAAV RRVGENAASI LTGEIDPISL LLHDGLLPKM YAEFRNQRCY HQIKAYIAEL
GLQNPSLRII EIGGGSASAS LPILQACNRD GQSSIAKYDF TDISSGFFLD ARKTLADYSE
IVDFHVLDIE QDASQQGIEK GSYDIVIACN VIHATVDIDV SLANAKGLLR PNGRLILMEI
TNPQPYYSLI FGAFPGWWAG AESGRVESPL LRGEQWSEKL IKHGFVDTEP VFRDFEEKQG
GTLGVFATTM AEDVSERKPI AHINIVGLPT APNAWSATDL ARVLGKSSEI SYIDLNDKSA
LLAPLRDAVI FLPEICDALT KSITEESFEA LQRQIIGSNI VLMLGRGGAI DPSLPNGSLT
TGFARTIRLE HPKVRFITLD LDPQSPYESS LTVVNEVLRS PVTDLSKPSA DLECEFAERN
GQLFVSRVVA EEKAEHYIKN ATGKSILHDR NFLSPRNAMR AGLGIVGLLE TFHWKPDPGM
DGPLGPDQVR VELRAASINF RDILVATGQV QSLTEMKNDC SGVVVESGEN MKSRFKPGDR
VCAYYGQSYS NFPVVDGDCC SRIPDSMSFE VAASVPIVWG TVYHSLVDIA HLAEGEKILI
HSGAGAVGQA AIALAQHLGA EVFTTAGSDQ KRAMLAEKFN LPNDHIFSSR NTHFKQGIKE
LTKGQGVDVI LNSLTGEMTR ASCEVLTDFG RFIEIGKKDL IDDALLPTKF LLRNITFACV
DLTQIIEKRH KQARRLLEKV VDLLASDAVK ATEITTYPIS EIEHAFRFVA SGKHIGKVIL
TVAQDEVVKV SSASEYLTKS YTDLVQAASA PPQLAQLQTD AVYIVVGGLG GLGRCVVPWL
ADRGARTIVT LSRSGASSEQ ATTLIEEMQS RGVSVVAKAC DIGSKESLRG VVEDIKGSLS
LPIRGLINSA MSLQDVTFKD MTHEQWQKSL LPKVQGTWNL HECLPKDLDF FISMSSIVAI
SGNLGQSNYG AACSFQDSFA AFRRAQGLSG YSINIGPVSD AGFVSENEQV NMGMERKGFS
SVTIAEVLAN LDYVVTSAGN RTQNSIGLLP ARPDASRSTW LQNKRLIHLA QHSGPRGEGE
GGKSDEAQDA LEAVGNATTA EGAEAAVLTA ILQQLSKLLM TPVEQLSPRR TLDSYGVDSL
IAVELKNWIG TYLEADIPLL VLRETNDIQH LARLAAEESR LVSLA
