Protein: N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase (EC 6.3.2.26) (Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase) (ACV synthetase) (ACVS) (P27742)
Organism: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
Function: Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic. The trimodular NRPS acvA produces the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) via condensation of the 3 residues L-2-aminoadipate, L-cysteine and L-valine. The precursor amino acids for penicillin biosynthesis are withdrawn from the vacuolar amino acid pool by the MFS-type transporter penV (By similarity). Each of the constituent amino acids of the tripeptide ACV are activated as aminoacyl-adenylates with peptide bonds formed through the participation of amino acid thioester intermediates. The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity).
Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P19787}. Vacuole membrane {ECO:0000250|UniProtKB:P19787}; Peripheral membrane protein {ECO:0000250|UniProtKB:P19787}. Note=Loosely attached to the vacuoles. {ECO:0000250|UniProtKB:P19787}.
Interaction partners:
- Isopenicillin N synthase
- Acyl-coenzyme A:6-aminopenicillanic-acid-acyltransferase 40 kDa form
Sequence:
MSPPGLLSEDGPGYSGGYADPTVPKVNWKQSNGKSAGGNGDVDAGNGNIDPSKSGVGVQVCFAGGLEGWKAGISKITERCDLSSIATNSTKYQLAVTGFSDGPDDYNEYSVPFPSEVLVAMEEMCLARDISMRSVIQFAVHYVLKGFGGGSHTVAASIDVGDDPNNIATSYTITPSIVCHESRQGQTVMQEIQSMEKLNQLRKQEMHPGEAGLSLIRMGLFDILVIFADANKCEGLIAGLPLAVMVCEGGGRLQVRIHFSGSLFRQKTLVDIAEALNVLFAKAASGGATPVRDLELLSAEQKQQLEEWNKTDGEYPECKRLNHLIEEATQLHEDKVAIVYKRRQLTYGELNAQANCFAHYLRSIGILPEQLVALFLEKSENLIVTILGIWKSGAAYVPIDPTYPDERVRFVLEDTQAKVIIASNHLAERLQSEVISDRELSIIRLEHCLSAIDQQPSTFPRANLRDPSLTSKQLAYVTYTSGTTGFPKGILKQHTNVVNSITDLSARYGVTGDHHEAILLFSAYVFEPFVRQMLMALVNGHLLAMVDDAEKYDAEKLIPFIREHKITYLNGTASVLQEYDFSSCPSLKRLILVGENLTESRYLALRRHFKNCILNEYGFTESAFVTALNVFEPGSARNNTSLGRPVRNVKCYILNKSLKRVPIGATGELHIGGLGISKGYLNRPDLTPQRFIPNPFQTDHEKELGLNQLMYKTGDLARWLPNGEIEYLGRADFQIKLRGIRIEPGEIESTLAGYPGVRTSLVVSKRLRHGEKETTNEHLVGYYVGDNTSVSETALLQFLELKLPRYMIPTRLVRVSQIPVTVNGKADLRALPSVDLIQPKVSSCELTDEVEIALGKIWADVLGAHHLSISRKDNFFRLGGHSITCIQLIARIRQQLGVIISIEDVFSSRTLERMAELLRSKESNGTPDERARPQLKTVAGEVANANVYLANSLQQGFVYQFLKNMGRSEAYVMQSVLRYDVNINPDLFKKAWKQVQHMLPTLRLRFQWGQDVLQVIDEDQPLNWWFLHLADDSALPEEQKLLELQRRDLAEPYDLAAGSLFRIYLIEHSSTRFSCLFSCHHAILDGWSLPLLFRKTHGTYLHLLHGHSLRTLEDPYRQSQQYLQDHREDHLRYWAGIVNQIEERCDMNALLNERSRYKIQLADYDKVEDQQQLTLTVPDASWLSKLRQTCSAQGITLHSILQFVWHAVLHAYGGGTHTVTGTTISGRNLPVSGIERSVGLYINTLPLVINQLAYKNKTVLEAIRDVQAIVNGMNSRGNVELGRLQKNELKHGLFDSLFVLENYPILDKSEEMRQKSELKYTIEGNIEKLDYPLAVIAREVDLTGGFTFTICYARELFDEIVISELLQMVRDTLLQVAKHLDDPVRSLEYLSSAQMAQLDAWNATDAEFPDTTLHAMFEKEAAQKPDKVAVVYEQRSLTYRQLNERANRMAHQLKSDISPKPNSIIALVVDKSEHMIATILAVWKTGGAYVPIDPEYPDDRIRYILEDTSAIAVISDACYLSRIQELAGESVRLYRSDISTQTDGNWSVSNPAPSSTSTDLAYIIYTSGTTGKPKGVMVEHHGVVNLQISLSKTFGLRDTDDEVILSFSNYVFDHFVEQMTDAILNGQTLVMLNDAMRSDKERLYQYIETNRVTYLSGTPSVISMYEFSRFKDHLRRVDCVGEAFSQPVFDQIRDTFQGLIINGYGPTEISITTHKRLYPFPERRTDKSIGQQIGNSTSYVLNADMKRVPIGAVGELYLGGEGVARGYHNRPEVTAERFLRNPFQTDSERQNGRNSRLYRTGDLVRWIPGSNGEIEYLGRNDFQVKIRGLRIELGEIEAVMSSHPDIKQSVVIAKSGKEGDQKFLVGYFVASSPLSPGAIRRFMQSRLPGYMIPSSFIPISSLPVTPSGKLDTKALPTAEEKGAMNVLAPRNEIESILCGIWAGLLDISAQTIGSDSDFFTLGGDSLKSTKLSFKIHEVFGRTISVSALFRHRTIESLAHLIMNNVGDIQEITPVDYDNRRKIAVSPAQERLLFIHELEGGGNAYNIDAAFELPPYIDQSRVEEALYTILSRHEALRTFLLRDQATGTFYQKILTTDEAKCMLIIEKSAVSTIDQIDSIVGRLSQHIFRLDSELPWLAHIVTHKTGNLYLTLSFHHTCFDAWSLKIFERELRVFCASNEKGGNMPILPMPQVQYKEYAEHHRRRLGKNQIQKLSDFWLQRLDGLEPLQLLPDYPRPAQFNYDGGDLSVILDGVVLETLRGIAKDHGVTLYAVLLAVYCLMLSTYTHQVDIAVGVPISHRTHPLFQSIVGFFVNMVVVRVDVKDFAVHDLIRRVMKALVDAQLHQDMPFQDVTKLLRVDNDASRHPLVQTVFNFESDMDKEFETTPSIQDTATIAPYQSVQRIKSVAKFDLNATATESGSALKINFNYATSLFRKETIQGFLETYRHLLLQLSYLGSQGLKEDTKLLLVRPEEMSGPHLPLAGLSNGAETLEAISLSRAFEFEAFRVPDRAAVVQGDKSLSYTELNKRANQLARYIQSVAHLRPDDKVLLILDKSIDMIICILAIWKTGSAYVPLDPSYPKERVQCISEVVQAKILITESRYASAWGSQTSTILAIDSPKVSNMVNNQATHNLPNIAGIKNLAYIIFTSGTSGKPKGVLVEQGGVLHLRDALRKRYFGIECNEYHAVLFLSNYVFDFSIEQLVLSIMSGHKLIIPEGEFVADDEFYITANGQRLSYLSGTPSLLQQIDLARLNHLQVVTAAGEQLHAAQFNKLRSGFRGPIYNAYGITETTVYNIVSEFSAQSQFENALRELLPGTRAYLLNHATQPVPMNAVGELYLAGDCVARGYLNQPVLTGDRFIQNPFQTEQDIASGSYPRLYRTGDLFRCRLDRQHQPYLEYLGRADLQVKIRGYRIEPSEVQNVLASCPGVRECAVVAKYENTDAYSRIAKFLVGYYTPDTETVSDSSILAHMKSKLPAYMVPKYLCRLEGGLPVTINGKLDVRKLPDIGNPQHQISYNPPRDVLEADLCRLWASALGTERCGIDDDLFRLGGDSITALHLAAQIHHQIGRKVTVRDIFDHPTIRGIHDNVMVKLVPHNVPQFQAEQQTVLGDAPLLPIQTWFLSKSLQHPSHWNHTFYLRTPELDVTTLSTAVAELQLYHDAFRMRLRQIDGRTVQCFADDISPVQLRVLNVKDVDGSAAIDQQLQKYQSDFDLEKGPICAAAYLHGYEDRSARVWFSVHHIIIDIVSWQILARDLQILYEGGTLGRKSSSVRQWAEALQSYQGSASERAYWEGLLAQTAANISALPPVTGTRTRLARTWSDDRTVILLNEASNQNASIQDLLLAAVGLALQQVTPGSPSMITLEGHGREEIVDPTLDLSRTLGWFTSMYPFEIPPLNVETLSQGIASLRECLRQVPARGIGFGSLYGYCKHQMPQVTFNYLGQLTSKQSITDQWALAVGDGEMQYGLTTSPADRDQSSFAVDITASCVNGALSVEMNSAWSLEKSMRFISRIEEVLNMILSGTLAQQATPVLTPQVFNEEMYTPYFEFSKTPRRGPILFLLPPGEGGAESYFNNIVKHLPTTNMVVFNNYYLHSKSLNTFEKLAEMYLGHIRQIQPDGPYHFIGWSFGGTIAMEISRQLVGLGSTIGLLGIIDTYFNVPGATRAIGLGDTEVLDPIHHISQPEPADFQCLPASTDYIILFKATRVNDKFQSENQRRLYEYYDKTLLNDLDWLLPGASNIHLVRLEEDTHFSWATNPRQIAHVCSTIEKFLARY