ID INPB_EMENI Reviewed; 2326 AA.
AC Q5B7I4; C8V545;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 27-NOV-2024, entry version 125.
DE RecName: Full=Nonribosomal peptide synthetase inpB {ECO:0000303|PubMed:20952652};
DE AltName: Full=Fellutamide B biosynthesis cluster protein B {ECO:0000303|PubMed:27294372};
DE AltName: Full=Inp cluster protein B {ECO:0000303|PubMed:20952652};
DE AltName: Full=Interacting NRPS system protein inpA {ECO:0000303|PubMed:18804170};
GN Name=inpB {ECO:0000303|PubMed:20952652}; ORFNames=ANIA_03496;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP IDENTIFICATION, FUNCTION, AND DOMAIN.
RX PubMed=18804170; DOI=10.1016/j.fgb.2008.08.008;
RA von Doehren H.;
RT "A survey of nonribosomal peptide synthetase (NRPS) genes in Aspergillus
RT nidulans.";
RL Fungal Genet. Biol. 46:S45-S52(2009).
RN [4]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20952652; DOI=10.1128/aem.00683-10;
RA Bergmann S., Funk A.N., Scherlach K., Schroeckh V., Shelest E., Horn U.,
RA Hertweck C., Brakhage A.A.;
RT "Activation of a silent fungal polyketide biosynthesis pathway through
RT regulatory cross talk with a cryptic nonribosomal peptide synthetase gene
RT cluster.";
RL Appl. Environ. Microbiol. 76:8143-8149(2010).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=27294372; DOI=10.1021/acschembio.6b00213;
RA Yeh H.H., Ahuja M., Chiang Y.M., Oakley C.E., Moore S., Yoon O.,
RA Hajovsky H., Bok J.W., Keller N.P., Wang C.C., Oakley B.R.;
RT "Resistance gene-guided genome mining: serial promoter exchanges in
RT Aspergillus nidulans reveal the biosynthetic pathway for fellutamide B, a
RT proteasome inhibitor.";
RL ACS Chem. Biol. 11:2275-2284(2016).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the inp gene cluster
CC that mediates the biosynthesis of fellutamide B, a mycotoxin that acts
CC as a proteasome inhibitor (PubMed:18804170, PubMed:20952652,
CC PubMed:27294372). In the first step of fellutabmide B biosynthesis inpC
CC activates 3-hydroxydodecanoic acid to generate 3-hydroxydodecanoyl-AMP
CC that is then loaded onto the T0 domain of inpB (PubMed:27294372). The
CC 3-hydroxydodecanoyl-S-phosphopantetheinyl-T0 is sequentially extended
CC with L-Asn and L-Gln by the two CAT modules of inpB (PubMed:27294372).
CC The linear lipodipeptide from inpB is then transferred onto inpA for
CC the addition of the third amino acid, L-Leu (PubMed:27294372).
CC Reductive releasing of the lipotripeptide by the TE domain of inpA
CC produces (2S)-fellutamide B (PubMed:27294372). InpF might be involved
CC in the release and transfer of the lipodipeptide from inpB to inpA
CC (PubMed:27294372). The inp cluster-encoded proteasome subunit inpE
CC confers resistance to internally produced fellutamides
CC (PubMed:27294372). The MFS efflux transporter inpD may contribute to
CC fellutamide resistance as well (PubMed:27294372).
CC {ECO:0000269|PubMed:27294372, ECO:0000305|PubMed:18804170,
CC ECO:0000305|PubMed:20952652}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:27294372}.
CC -!- INDUCTION: Expression is positively regulated by the secondary
CC metabolism cross-pathway regulator scpR (PubMed:20952652).
CC {ECO:0000269|PubMed:20952652}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module (By similarity). Each module is responsible for the recognition
CC (via the A domain) and incorporation of a single amino acid into the
CC growing peptide product (By similarity). Thus, an NRP synthetase is
CC generally composed of one or more modules and can terminate in a
CC thioesterase domain (TE) that releases the newly synthesized peptide
CC from the enzyme (By similarity). Occasionally, methyltransferase
CC domains (responsible for amino acid methylation) are present within the
CC NRP synthetase (By similarity). InpB has the following architecture:
CC T0-C-A-T-C-A-T (PubMed:18804170). {ECO:0000250|UniProtKB:A0A144KPJ6,
CC ECO:0000305|PubMed:18804170}.
CC -!- DISRUPTION PHENOTYPE: Eliminates the production of fellutamides
CC (PubMed:27294372). Does not impair the production of asperfuranone
CC (PubMed:20952652). {ECO:0000269|PubMed:20952652,
CC ECO:0000269|PubMed:27294372}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; BN001302; CBF76036.1; -; Genomic_DNA.
DR RefSeq; XP_661100.1; XM_656008.1.
DR AlphaFoldDB; Q5B7I4; -.
DR SMR; Q5B7I4; -.
DR STRING; 227321.Q5B7I4; -.
DR EnsemblFungi; CBF76036; CBF76036; ANIA_03496.
DR GeneID; 2872918; -.
DR KEGG; ani:ANIA_03496; -.
DR VEuPathDB; FungiDB:AN3496; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_4_1; -.
DR InParanoid; Q5B7I4; -.
DR OMA; CTPISTI; -.
DR OrthoDB; 2787863at2759; -.
DR Proteomes; UP000000560; Chromosome II.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IBA:GO_Central.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IBA:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; IEP:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR CDD; cd05918; A_NRPS_SidN3_like; 2.
DR CDD; cd19542; CT_NRPS-like; 1.
DR CDD; cd19545; FUM14_C_NRPS-like; 1.
DR FunFam; 3.40.50.980:FF:000001; Non-ribosomal peptide synthetase; 1.
DR FunFam; 2.30.38.10:FF:000009; Nonribosomal peptide synthase inpB; 1.
DR FunFam; 3.30.300.30:FF:000116; Nonribosomal peptide synthase inpB; 1.
DR FunFam; 3.30.559.10:FF:000048; Nonribosomal peptide synthase inpB; 1.
DR FunFam; 3.30.300.30:FF:000015; Nonribosomal peptide synthase SidD; 1.
DR FunFam; 3.30.559.30:FF:000003; Nonribosomal peptide synthase SidD; 1.
DR FunFam; 1.10.1200.10:FF:000005; Nonribosomal peptide synthetase 1; 2.
DR FunFam; 3.40.50.12780:FF:000014; Nonribosomal peptide synthetase 1; 2.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.40.50.980; -; 2.
DR Gene3D; 1.10.1200.10; ACP-like; 3.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 2.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation domain; 2.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig_com.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR NCBIfam; TIGR01733; AA-adenyl-dom; 2.
DR PANTHER; PTHR45527:SF1; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR45527; NONRIBOSOMAL PEPTIDE SYNTHETASE; 1.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 2.
DR SUPFAM; SSF47336; ACP-like; 3.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 4.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 2: Evidence at transcript level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome.
FT CHAIN 1..2326
FT /note="Nonribosomal peptide synthetase inpB"
FT /id="PRO_0000444109"
FT DOMAIN 8..84
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:18804170"
FT DOMAIN 1145..1221
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:18804170"
FT DOMAIN 2216..2294
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:18804170"
FT REGION 87..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 144..568
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18804170"
FT REGION 593..997
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18804170"
FT REGION 1226..1247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1266..1680
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18804170"
FT REGION 1702..2097
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18804170"
FT COMPBIAS 105..121
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 45
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1182
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2253
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2326 AA; 253076 MW; 03AED830E5FDD3AA CRC64;
MPGAIESSPS EWLQLELRRI CANVLQLDTK DVDPQRSFLS LGGDSLLAIK ILAQCRAQGI
TINIADIMAA TTLESLYSMA QGPAELASSS TSDNASDKDS SLDDSETGAL TPTTDAGSSL
ADTLSPEMKA KLSALSVSQD TAIQAVVPCS AIQDRMLVSQ LQNPHLYSCC FVLRLTHSHP
GLPVDAKRLG TAWGEVVKRH SSLRTVLVES TQRPGHYNQV ILAGIIPAVE HYEGADHLGS
VKFNVNNPIV FQPHSIPHRL QLVQVSPSEV YLKFDISHLL IDGQSAEVLL KDLSDAYRDG
GLAAAPLSYA DYVSSYLLEP AQLNTSRKES GMEMSPLTVP MDRPNEGLFD FQTVSANVPL
DSRLVQSVCA RYSVTLATVC QLAWGLVLRC YAGTDSVCFS YVNSGRSMSI PGVQEVIGPI
VQTSMCSIQL GPADELPKIL QRIHRDALQA MSQLSPLEAN STSKSARQLS NTTMSFQRAL
DDAAAQRAGL LVKIEGKANP TDYDISLGIA AGADGLSVDL DFWGSRLDEE SARTMLGAFE
AAIRGIIDSP DSTVSNISLL SPGEVSQLAQ WNASIPKPER VCVHDKIMEI SKLQPGAAAV
NSWDGNLTYH DLTVQASTLA HHLRDQLGVG PERFVGICMD KSKWAIVSML AVLMAGGIVV
PLGVSHPRAR IRELLNDTAA VALLVDGKHG DRLAGLEVEN AAMLTVDQQL LDSLPTIPKP
PVSGVTPDNA AWVIYTSGST GVPKGVVLLH QNISTSVIAH GAVFGVNCVT RTAQFASYTF
DVSLSDIVMT LFHGGCVCIF SEESRMNSLT EALQGLAVNY VNLTPTVLGL LNPADLPVIR
TVVAGGEAMD PGIIEKWSPH ARVFNSVGPS ECTIIAVAAG PVTDPAQAAN VGYPTGTRLW
VALPTDPNQL CPVGVPGELL IEGPMLSRGY LNDPEKTAGA FITNPAFVKH LEAATPAWKV
LFQKSERRFY RSGDLVRQKR DGSLVHMGRR DTQVKIRGQR VEIGEIEYWI MQRLKEVRRV
AVLVIERGQG KEQKSLVAAV EFKEDYEDVR HSDDDISPVT KIGESTVLPQ LLPLTEPLSK
ALHQLRNDLL EHLPPYMSPT MYAPVSQLPL NLSGKIDRRA VTQFINELDD VQLQQYLAVS
GSHQEPSTET EFKLQKLWAK TLGVDVSQIS ADSHFFHIGG DSVAAMRVVA AARDVELVLR
VADLFEYPRL PDLARAVESR VVDEADEEDP APFSVWRESR GSEPSEEPVE LDKIAAMCNL
SKEQIEDVLP CTALQEGLIA LTAQQPTAYI DRRVFALSQE VDLSQYRAAW QIVIHRTSAL
RTRIVSGPQT GSLQVVVVPR HIDWNKSSSL DEYLETDRQT GMMMGQPLNR FAFVDQPDGQ
RFFVWTTHHS TYDGWSRALV LQQVADAYAS RDLPPIASFS RFIQYIHSQP QDAAASYWKA
QLGGDTSADF PALPIANYRP RPQQRHQHTV NLASSSTKVM LPDLLRGAWA LVVHQYVGKT
DPVFAIALSG RNAPVRNVPN IAGPTLTTVP VRIFIDPEQL VNEFLQSVRQ QAVDMIPYEH
TGLQRIKKMV PELAAAVDLK HLFVVQPASD GESKFKIPGV TEHLVAVDEF DSYGLNVECM
LSGQSIEVDV RFDEKMLSSS QVIRLMSQFE AVVHQLHLHG EGSLKIKDID LLSPEDVNQL
RQWNALPLAQ PLDVCLHDLI AEVARSRPGA AAIEAWDGTL THAQLQSYAS TLAGYLIELG
VGPEISVPVC MDKSVWAVVC FLAVLQAGGV VVPLGTGHPI PHIASIIEDT GAKLVLVDAQ
QFERLLELTP SRGLTLVPID TQLLNSLPTA APQTSVTPAN AAWIVFTSGS TGKAKGVVLT
HSNLSTAIKT HGARFGLGTH TRTIQFAAHT FDAVLQDYFT TLASGGTVCV PSEADRMNDL
AGVMRGMNVN FANLTSTVAR LLTPDQVPSL KVLILAGEQI QDSVVETWYK HAEVLNVYGP
TECSINSTCN GPISDLSNAQ SIGFGMGSRT WIADPTDPNR LCPVGTPGEL LIEGPGLARG
YLGDPAKTEA AIIQNPSFAS RFALSDCRVY RTGDLAKQTE DGQILYLGRI DTQIKIRGQR
VELGEIEHWI GRHLPHVKHT AVVAISRGEK QMRLAAVIER ENGHKPDPVI FTQLKKTLSS
LLPSYMVPSL YIPVTEIPLT VSGKLDRRAI KQTVESMPTE ELEQYFAGES SGTRVPPSTE
MEKALQRIWA NSLGIEVDAI GADDNFFQLG GDSVVAMHIS ASSRQDQSVK GLAVGDIFMH
PRLADLAVLL EKRPREGEGG WDEEMRDDES PFALLQEVLD LDLKDI
//
