Protein: Nonribosomal peptide synthetase inpB (Fellutamide B biosynthesis cluster protein B) (Inp cluster protein B) (Interacting NRPS system protein inpA) (Q5B7I4)
Organism: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
Function: Nonribosomal peptide synthase; part of the inp gene cluster that mediates the biosynthesis of fellutamide B, a mycotoxin that acts as a proteasome inhibitor. In the first step of fellutabmide B biosynthesis inpC activates 3-hydroxydodecanoic acid to generate 3-hydroxydodecanoyl-AMP that is then loaded onto the T0 domain of inpB. The 3-hydroxydodecanoyl-S-phosphopantetheinyl-T0 is sequentially extended with L-Asn and L-Gln by the two CAT modules of inpB. The linear lipodipeptide from inpB is then transferred onto inpA for the addition of the third amino acid, L-Leu. Reductive releasing of the lipotripeptide by the TE domain of inpA produces (2S)-fellutamide B. InpF might be involved in the release and transfer of the lipodipeptide from inpB to inpA. The inp cluster-encoded proteasome subunit inpE confers resistance to internally produced fellutamides. The MFS efflux transporter inpD may contribute to fellutamide resistance as well.
Interaction partners:
- Acyl-CoA ligase inpC
- C2H2-type zinc-finger transcription factor
- Esterase inpF
Sequence:
MPGAIESSPSEWLQLELRRICANVLQLDTKDVDPQRSFLSLGGDSLLAIKILAQCRAQGITINIADIMAATTLESLYSMAQGPAELASSSTSDNASDKDSSLDDSETGALTPTTDAGSSLADTLSPEMKAKLSALSVSQDTAIQAVVPCSAIQDRMLVSQLQNPHLYSCCFVLRLTHSHPGLPVDAKRLGTAWGEVVKRHSSLRTVLVESTQRPGHYNQVILAGIIPAVEHYEGADHLGSVKFNVNNPIVFQPHSIPHRLQLVQVSPSEVYLKFDISHLLIDGQSAEVLLKDLSDAYRDGGLAAAPLSYADYVSSYLLEPAQLNTSRKESGMEMSPLTVPMDRPNEGLFDFQTVSANVPLDSRLVQSVCARYSVTLATVCQLAWGLVLRCYAGTDSVCFSYVNSGRSMSIPGVQEVIGPIVQTSMCSIQLGPADELPKILQRIHRDALQAMSQLSPLEANSTSKSARQLSNTTMSFQRALDDAAAQRAGLLVKIEGKANPTDYDISLGIAAGADGLSVDLDFWGSRLDEESARTMLGAFEAAIRGIIDSPDSTVSNISLLSPGEVSQLAQWNASIPKPERVCVHDKIMEISKLQPGAAAVNSWDGNLTYHDLTVQASTLAHHLRDQLGVGPERFVGICMDKSKWAIVSMLAVLMAGGIVVPLGVSHPRARIRELLNDTAAVALLVDGKHGDRLAGLEVENAAMLTVDQQLLDSLPTIPKPPVSGVTPDNAAWVIYTSGSTGVPKGVVLLHQNISTSVIAHGAVFGVNCVTRTAQFASYTFDVSLSDIVMTLFHGGCVCIFSEESRMNSLTEALQGLAVNYVNLTPTVLGLLNPADLPVIRTVVAGGEAMDPGIIEKWSPHARVFNSVGPSECTIIAVAAGPVTDPAQAANVGYPTGTRLWVALPTDPNQLCPVGVPGELLIEGPMLSRGYLNDPEKTAGAFITNPAFVKHLEAATPAWKVLFQKSERRFYRSGDLVRQKRDGSLVHMGRRDTQVKIRGQRVEIGEIEYWIMQRLKEVRRVAVLVIERGQGKEQKSLVAAVEFKEDYEDVRHSDDDISPVTKIGESTVLPQLLPLTEPLSKALHQLRNDLLEHLPPYMSPTMYAPVSQLPLNLSGKIDRRAVTQFINELDDVQLQQYLAVSGSHQEPSTETEFKLQKLWAKTLGVDVSQISADSHFFHIGGDSVAAMRVVAAARDVELVLRVADLFEYPRLPDLARAVESRVVDEADEEDPAPFSVWRESRGSEPSEEPVELDKIAAMCNLSKEQIEDVLPCTALQEGLIALTAQQPTAYIDRRVFALSQEVDLSQYRAAWQIVIHRTSALRTRIVSGPQTGSLQVVVVPRHIDWNKSSSLDEYLETDRQTGMMMGQPLNRFAFVDQPDGQRFFVWTTHHSTYDGWSRALVLQQVADAYASRDLPPIASFSRFIQYIHSQPQDAAASYWKAQLGGDTSADFPALPIANYRPRPQQRHQHTVNLASSSTKVMLPDLLRGAWALVVHQYVGKTDPVFAIALSGRNAPVRNVPNIAGPTLTTVPVRIFIDPEQLVNEFLQSVRQQAVDMIPYEHTGLQRIKKMVPELAAAVDLKHLFVVQPASDGESKFKIPGVTEHLVAVDEFDSYGLNVECMLSGQSIEVDVRFDEKMLSSSQVIRLMSQFEAVVHQLHLHGEGSLKIKDIDLLSPEDVNQLRQWNALPLAQPLDVCLHDLIAEVARSRPGAAAIEAWDGTLTHAQLQSYASTLAGYLIELGVGPEISVPVCMDKSVWAVVCFLAVLQAGGVVVPLGTGHPIPHIASIIEDTGAKLVLVDAQQFERLLELTPSRGLTLVPIDTQLLNSLPTAAPQTSVTPANAAWIVFTSGSTGKAKGVVLTHSNLSTAIKTHGARFGLGTHTRTIQFAAHTFDAVLQDYFTTLASGGTVCVPSEADRMNDLAGVMRGMNVNFANLTSTVARLLTPDQVPSLKVLILAGEQIQDSVVETWYKHAEVLNVYGPTECSINSTCNGPISDLSNAQSIGFGMGSRTWIADPTDPNRLCPVGTPGELLIEGPGLARGYLGDPAKTEAAIIQNPSFASRFALSDCRVYRTGDLAKQTEDGQILYLGRIDTQIKIRGQRVELGEIEHWIGRHLPHVKHTAVVAISRGEKQMRLAAVIERENGHKPDPVIFTQLKKTLSSLLPSYMVPSLYIPVTEIPLTVSGKLDRRAIKQTVESMPTEELEQYFAGESSGTRVPPSTEMEKALQRIWANSLGIEVDAIGADDNFFQLGGDSVVAMHISASSRQDQSVKGLAVGDIFMHPRLADLAVLLEKRPREGEGGWDEEMRDDESPFALLQEVLDLDLKDI