Protein: N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase (ACV synthetase) (ACVS) (EC 6.3.2.26) (Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase) (Nonribosomal peptide synthetase acvA) (Penicillin biosynthetis cluster p rotein acvA) (P19787)
Organism: Penicillium chrysogenum (Penicillium notatum)
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 The precursor amino acids for penicillin biosynthesis are withdrawn from the vacuolar amino acid pool by the MFS-type transporter penV. 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 aatA to yield penicillin in the peroxisomal matrix (Probable).
Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:12223189}. Vacuole membrane {ECO:0000269|PubMed:1899377, ECO:0000269|PubMed:8416970}; Peripheral membrane protein {ECO:0000269|PubMed:8416970}. Note=Loosely attached to the vacuoles. {ECO:0000269|PubMed:8416970}.
Interaction partners:
Sequence:
MGPSNPAMAYFKPSTRDTMDPCSGNAADGSIRVRFRGGIERWKECVNQVPERCDLSGLTTDSTRYQLASTGFGDASAAYQERLMTVPVDVHAALQELCLERRVSVGSVINFSVHQMLKGFGNGTHTITASLHREQNLQNSSPSWVVSPTIVTHENRDGWSVAQAVESIEAGRGSEKESVTAIDSGSSLVKMGLFDLLVSFVDADDARIPCFDFPLAVIVRECDANLSLTLRFSDCLFNEETICNFTDALNILLAEAVIGRVTPVADIELLSAEQKQQLEEWNNTDGEYPSSKRLHHLIEEVVERHEDKIAVVCDERELTYGELNAQGNSLARYLRSIGILPEQLVALFLDKSEKLIVTILGVWKSGAAYVPIDPTYPDERVRFVLDDTKARAIIASNQHVERLQREVIGDRNLCIIRLEPLLASLAQDSSKFPAHNLDDLPLTSQQLAYVTYTSGTTGFPKGIFKQHTNVVNSITDLSARYGVAGQHHEAILLFSACVFEPFVRQTLMALVNGHLLAVINDVEKYDADTLLPFIRRHSITYLNGTASVLQEYDFSDCPSLNRIILVGENLTEARYLALRQRFKNRILNEYGFTESAFVTALKIFDPESTRKDTSLGRPVRNVKCYILNPSLKRVPIGATGELHIGGLGISKGYLNRPELTPHRFIPNPFQTDCEKQLGINSLMYKTGDLARWLPNGEVEYLGRADFQIKLRGIRIEPGEIETMLAMYPRVRTSLVVSKKLRNGPEETTNEHLVGYYVCDSASVSEADLLSFLEKKLPRYMIPTRLVQLSQIPVNVNGKADLRALPAVDISNSTEVRSDLRGDTEIALGEIWADVLGARQRSVSRNDNFFRLGGHSITCIQLIARIRQRLSVSISVEDVFATRTLERMADLLQNKQQEKCDKPHEAPTELLEENAATDNIYLANSLQQGFVYHYLKSMEQSDAYVMQSVLRYNTTLSPDLFQRAWKHAQQSFPALRLRFSWEKEVFQLLDQDPPLDWRFLYFTDVAAGAVEDRKLEDLRRQDLTERFKLDVGRLFRVYLIKHSENRFTCLFSCHHAILDGWSLPLLFEKVHETYLQLLHGDNLTSSMDDPYTRTQRYLHAHREDHLDFWAGVVQKINERCDMNALLNERSRYKVQLADYDQVQEQRQLTIALSGDAWLADLRQTCSAQGITLHSILQFVWHAVLHAYGGGTHTITGTTISGRNLPILGIERAVGPYINTLPLVLDHSTFKDKTIMEAIEDVQAKVNVMNSRGNVELGRLHKTDLKHGLFDSLFVLENYPNLDKSRTLEHQTELGYSIEGGTEKLNYPLAVIAREVETTGGFTVSICYASELFEEVMISELLHMVQDTLMQVARGLNEPVGSLEYLSSIQLEQLAAWNATEAEFPDTTLHEMFENEASQKPDKIAVVYEETSLTYRELNERANRMAHQLRSDVSPNPNEVIALVMDKSEHMIVNILAVWKSGGAYVPIDPGYPNDRIQYILEDTQALAVIADSCYLPRIKGMAASGTLLYPSVLPANPDSKWSVSNPSPLSRSTDLAYIIYTSGTTGRPKGVTVEHHGVVNLQVSLSKVFGLRDTDDEVILSFSNYVFDHFVEQMTDAILNGQTLLVLNDGMRGDKERLYRYIEKNRVTYLSGTPSVVSMYEFSRFKDHLRRVDCVGEAFSEPVFDKIRETFHGLVINGYGPTEVSITTHKRLYPFPERRMDKSIGQQVHNSTSYVLNEDMKRTPIGSVGELYLGGEGVVRGYHNRADVTAERFIPNPFQSEEDKREGRNSRLYKTGDLVRWIPGSSGEVEYLGRNDFQVKIRGLRIELGEIEAILSSYHGIKQSVVIAKDCREGAQKFLVGYYVADAALPSAAIRRFMQSRLPGYMVPSRLILVSKFPVTPSGKLDTKALPPAEEESEIDVVPPRSEIERSLCDIWAELLEMHPEEIGIYSDFFSLGGDSLKSTKLSFMIHESFNRAVSVSALFCHRTVEAQTHLILNDAADVHEITPIDCNDTQMIPVSRAQERLLFIHEFENGSNAYNIDAAFELPGSVDASLLEQALRGNLARHEALRTLLVKDHATGIYLQKVLSPDEAQGMFSVNVDTAKQVERLDQEIASLSQHVFRLDDELPWEARILKLESGGLYLILAFHHTCFDAWSLKVFEQELRALYAALQKTKSAANLPALKAQYKEYALYHRRQLSGDRMRNLSDFWLRKLIGLEPLQLITDRPRPVQFKYDGDDLSIELSKKETENLRGVAKRCKSSLYVVLVSVYCVMLASYANQSDVSVGIPVSHRTHPQFQSVIGFFVNLVVLRVDISQSAICGLIRRVMKELVDAQLHQDMPFQEVTKLLQVDNDPSRHPLVQNVFNFESRANGEHDARSEDEGSLAFNQYRPVQPVDSVAKFDLNATVTELESGLRVNFNYATSLFNKSTIQGFLHTYEYLLRQLSELSAEGINEDTQLSLVRPTENGDLHLPLAQSPLATTAEEQKVASLNQAFEREAFLAAEKIAVVQGDRALSYADLNGQANQLARYIQSVSCIGADDGIALMLEKSIDTIICILAIWKAGAAYVPLDPTYPPGRVQLILEEIKAKAVLVHSSHASKCERHGAKVIAVDSPAIETAVSQQSAADLPTIASLGNLAYIIFTSGTSGKPKGVLVEQKAVLLLRDALRERYFGRDCTKHHGVLFLSNYVFDFSVEQLVLSVLSGHKLIVPPAEFVADDEFYRMASTHGLSYLSGTPSLLQKIDLARLDHLQVVTAAGEELHATQYEKMRRRFNGPIYNAYGVTETTVYNIIAEFTTNSIFENALREVLPGTRAYVLNAALQPVPFDAVGELYLAGDSVTRGYLNQPLLTDQRFIPNPFCKEEDIAMGRFARLYKTGDLVRSRFNRQQQPQLEYLGRGDLQIKMRGYRIEISEVQNVLTSSPGVREGAVVAKYENNDTYSRTAHSLVGYYTTDNETVSEADILTFMKARLPTYMVPSHLCCLEGALPVTINGKLDVRRLPEIINDSAQSSYSPPRNIIEAKMCRLWESALGMERCGIDDDLFKLGGDSITSLHLVAQIHNQVGCKITVRDIFEHRTARALHDHVFMKDSDRSNVTQFRTEQGPVIGEAPLLPIQDWFLSKALQHPMYWNHTFYVRTPELDVDSLSAAVRDLQQYHDVFRMRLKREEVGFVQSFAEDFSPAQLRVLNVKDVDGSAAVNEILDGWQSGFNLENGPIGSIGYLHGYEDRSARVWFSVHHMAIDTVSWQILVRDLQTLYRNGSLGSKGSSFRQWAEAIQNYKASDSERNHWNKLVMETASSISALPTSTGSRVRLSRSLSPEKTASLIQGGIDRQDVSVYDSLLTSVGLALQHIAPTGPSMVTIEGHGREEVDQTLDVSRTMGWFTTMYPFEIPRLSTENIVQGVVAVSERFRQVPARGVGYGTLYGYTQHPLPQVTVNYLGQLARKQSKPKEWVLAVGDNEFEYGLMTSPEDKDRSSSAVDVTAVCIDGTMIIDVDSAWSLEESEQFISSIEEGLNKILDGRASQQTSRFPDVPQPAETYTPYFEYLEPPRQGPTLFLLPPGEGGAESYFNNIVKRLRQTNMVVFNNYYLHSKRLRTFEELAEMYLDQVRGIQPHGPYHFIGWSFGGILAMEMSRRLVASDEKIGFLGIIDTYFNVRGATRTIGLGDTEILDPIHHIYNPDPANFQRLPSATDRIVLFKAMRPNNKYESENQRRLYEYYDGTRLNGLDSLLPSDSDVQLVPLTDDTHFSWVGNPQQVEQMCATIKEHLARY