P19787 · ACVA_PENCH

Function

function

Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:1368505, PubMed:21889568, PubMed:9266851).
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 (PubMed:19686863, PubMed:21889568, PubMed:9266851, PubMed:9355751).
The precursor amino acids for penicillin biosynthesis are withdrawn from the vacuolar amino acid pool by the MFS-type transporter penV (PubMed:22777282, PubMed:8416970).
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 (PubMed:21889568, PubMed:9266851).
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) (PubMed:1368505).

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
pantetheine 4'-phosphate (UniProtKB | Rhea| CHEBI:47942 )
Note: Binds 3 phosphopantetheines covalently.
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
46 μML-2-aminoadipate
80 μML-cysteine
83 μML-valine

pH Dependence

Optimum pH is 8.4.

Pathway

Antibiotic biosynthesis; penicillin G biosynthesis; penicillin G from L-alpha-aminoadipate and L-cysteine and L-valine: step 1/3.

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentvacuolar membrane
Molecular FunctionATP binding
Molecular FunctionN-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase activity
Molecular Functionphosphopantetheine binding
Biological Processamino acid activation for nonribosomal peptide biosynthetic process
Biological Processpenicillin biosynthetic process

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
  • EC number
  • Short names
    ACV synthetase
    ; ACVS
  • Alternative names
    • Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase
    • Nonribosomal peptide synthetase acvA
    • Penicillin biosynthetis cluster p rotein acvA

Gene names

    • Name
      acvA
    • Synonyms
      pcbAB

Organism names

  • Taxonomic identifier
  • Strains
    • AS-P-78
    • CMI 314652
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Penicillium > Penicillium chrysogenum species complex

Accessions

  • Primary accession
    P19787
  • Secondary accessions
    • P26046

Subcellular Location

Cytoplasm, cytosol
Vacuole membrane
; Peripheral membrane protein
Note: Loosely attached to the vacuoles.

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis3339-3344Impairs epimerase activity and blocks tripeptide ACV production.
Mutagenesis3599Impairs tripeptide ACV production.

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00001930601-3746N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
Modified residue855O-(pantetheine 4'-phosphoryl)serine
Modified residue1939O-(pantetheine 4'-phosphoryl)serine
Modified residue3026O-(pantetheine 4'-phosphoryl)serine

Keywords

Expression

Induction

Expression is repressed by glucose (PubMed:3096965).
The transcription factor rfx1 controls penicillin biosynthesis through the regulation of the acvA, ipnA and aatA transcription (PubMed:22960281).
The promoter heptameric sequence 5'-TTAGTAA-3' is the binding site for the transcriptional activator named penicillin transcriptional activator 1 (PTA1) (PubMed:10644695).
Multiple additional DNA-binding proteins appear to bind to the promoter, including the nuclear factor A (NF-A) that recognizes an the 5'-GCCAAGCC-3' sequence or the global-acting nitrogen regulatory protein NIT2 that binds strongly at a single site that contains two closely spaced GATA sequences (PubMed:7614558).

Structure

3D structure databases

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region299-711Adenylation (A) domain 1
Domain818-895Carrier 1
Region918-1372Condensation (C) domain 1
Region1391-1801Adenylation (A) domain 2
Domain1902-1979Carrier 2
Region1994-2434Condensation (C) domain 2
Region2478-2883Adenylation (A) domain 3
Domain2991-3066Carrier 3
Region3084-3500Epimerase (E) domain
Region3530-3732Thioesterase (TE) domain

Domain

NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. GliP has the following architecture: A-T-C-A-T-C-A-T-E-TE.

Sequence similarities

Belongs to the NRP synthetase family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    3,746
  • Mass (Da)
    421,076
  • Last updated
    1991-02-01 v1
  • Checksum
    449BCC73253ED589
MGPSNPAMAYFKPSTRDTMDPCSGNAADGSIRVRFRGGIERWKECVNQVPERCDLSGLTTDSTRYQLASTGFGDASAAYQERLMTVPVDVHAALQELCLERRVSVGSVINFSVHQMLKGFGNGTHTITASLHREQNLQNSSPSWVVSPTIVTHENRDGWSVAQAVESIEAGRGSEKESVTAIDSGSSLVKMGLFDLLVSFVDADDARIPCFDFPLAVIVRECDANLSLTLRFSDCLFNEETICNFTDALNILLAEAVIGRVTPVADIELLSAEQKQQLEEWNNTDGEYPSSKRLHHLIEEVVERHEDKIAVVCDERELTYGELNAQGNSLARYLRSIGILPEQLVALFLDKSEKLIVTILGVWKSGAAYVPIDPTYPDERVRFVLDDTKARAIIASNQHVERLQREVIGDRNLCIIRLEPLLASLAQDSSKFPAHNLDDLPLTSQQLAYVTYTSGTTGFPKGIFKQHTNVVNSITDLSARYGVAGQHHEAILLFSACVFEPFVRQTLMALVNGHLLAVINDVEKYDADTLLPFIRRHSITYLNGTASVLQEYDFSDCPSLNRIILVGENLTEARYLALRQRFKNRILNEYGFTESAFVTALKIFDPESTRKDTSLGRPVRNVKCYILNPSLKRVPIGATGELHIGGLGISKGYLNRPELTPHRFIPNPFQTDCEKQLGINSLMYKTGDLARWLPNGEVEYLGRADFQIKLRGIRIEPGEIETMLAMYPRVRTSLVVSKKLRNGPEETTNEHLVGYYVCDSASVSEADLLSFLEKKLPRYMIPTRLVQLSQIPVNVNGKADLRALPAVDISNSTEVRSDLRGDTEIALGEIWADVLGARQRSVSRNDNFFRLGGHSITCIQLIARIRQRLSVSISVEDVFATRTLERMADLLQNKQQEKCDKPHEAPTELLEENAATDNIYLANSLQQGFVYHYLKSMEQSDAYVMQSVLRYNTTLSPDLFQRAWKHAQQSFPALRLRFSWEKEVFQLLDQDPPLDWRFLYFTDVAAGAVEDRKLEDLRRQDLTERFKLDVGRLFRVYLIKHSENRFTCLFSCHHAILDGWSLPLLFEKVHETYLQLLHGDNLTSSMDDPYTRTQRYLHAHREDHLDFWAGVVQKINERCDMNALLNERSRYKVQLADYDQVQEQRQLTIALSGDAWLADLRQTCSAQGITLHSILQFVWHAVLHAYGGGTHTITGTTISGRNLPILGIERAVGPYINTLPLVLDHSTFKDKTIMEAIEDVQAKVNVMNSRGNVELGRLHKTDLKHGLFDSLFVLENYPNLDKSRTLEHQTELGYSIEGGTEKLNYPLAVIAREVETTGGFTVSICYASELFEEVMISELLHMVQDTLMQVARGLNEPVGSLEYLSSIQLEQLAAWNATEAEFPDTTLHEMFENEASQKPDKIAVVYEETSLTYRELNERANRMAHQLRSDVSPNPNEVIALVMDKSEHMIVNILAVWKSGGAYVPIDPGYPNDRIQYILEDTQALAVIADSCYLPRIKGMAASGTLLYPSVLPANPDSKWSVSNPSPLSRSTDLAYIIYTSGTTGRPKGVTVEHHGVVNLQVSLSKVFGLRDTDDEVILSFSNYVFDHFVEQMTDAILNGQTLLVLNDGMRGDKERLYRYIEKNRVTYLSGTPSVVSMYEFSRFKDHLRRVDCVGEAFSEPVFDKIRETFHGLVINGYGPTEVSITTHKRLYPFPERRMDKSIGQQVHNSTSYVLNEDMKRTPIGSVGELYLGGEGVVRGYHNRADVTAERFIPNPFQSEEDKREGRNSRLYKTGDLVRWIPGSSGEVEYLGRNDFQVKIRGLRIELGEIEAILSSYHGIKQSVVIAKDCREGAQKFLVGYYVADAALPSAAIRRFMQSRLPGYMVPSRLILVSKFPVTPSGKLDTKALPPAEEESEIDVVPPRSEIERSLCDIWAELLEMHPEEIGIYSDFFSLGGDSLKSTKLSFMIHESFNRAVSVSALFCHRTVEAQTHLILNDAADVHEITPIDCNDTQMIPVSRAQERLLFIHEFENGSNAYNIDAAFELPGSVDASLLEQALRGNLARHEALRTLLVKDHATGIYLQKVLSPDEAQGMFSVNVDTAKQVERLDQEIASLSQHVFRLDDELPWEARILKLESGGLYLILAFHHTCFDAWSLKVFEQELRALYAALQKTKSAANLPALKAQYKEYALYHRRQLSGDRMRNLSDFWLRKLIGLEPLQLITDRPRPVQFKYDGDDLSIELSKKETENLRGVAKRCKSSLYVVLVSVYCVMLASYANQSDVSVGIPVSHRTHPQFQSVIGFFVNLVVLRVDISQSAICGLIRRVMKELVDAQLHQDMPFQEVTKLLQVDNDPSRHPLVQNVFNFESRANGEHDARSEDEGSLAFNQYRPVQPVDSVAKFDLNATVTELESGLRVNFNYATSLFNKSTIQGFLHTYEYLLRQLSELSAEGINEDTQLSLVRPTENGDLHLPLAQSPLATTAEEQKVASLNQAFEREAFLAAEKIAVVQGDRALSYADLNGQANQLARYIQSVSCIGADDGIALMLEKSIDTIICILAIWKAGAAYVPLDPTYPPGRVQLILEEIKAKAVLVHSSHASKCERHGAKVIAVDSPAIETAVSQQSAADLPTIASLGNLAYIIFTSGTSGKPKGVLVEQKAVLLLRDALRERYFGRDCTKHHGVLFLSNYVFDFSVEQLVLSVLSGHKLIVPPAEFVADDEFYRMASTHGLSYLSGTPSLLQKIDLARLDHLQVVTAAGEELHATQYEKMRRRFNGPIYNAYGVTETTVYNIIAEFTTNSIFENALREVLPGTRAYVLNAALQPVPFDAVGELYLAGDSVTRGYLNQPLLTDQRFIPNPFCKEEDIAMGRFARLYKTGDLVRSRFNRQQQPQLEYLGRGDLQIKMRGYRIEISEVQNVLTSSPGVREGAVVAKYENNDTYSRTAHSLVGYYTTDNETVSEADILTFMKARLPTYMVPSHLCCLEGALPVTINGKLDVRRLPEIINDSAQSSYSPPRNIIEAKMCRLWESALGMERCGIDDDLFKLGGDSITSLHLVAQIHNQVGCKITVRDIFEHRTARALHDHVFMKDSDRSNVTQFRTEQGPVIGEAPLLPIQDWFLSKALQHPMYWNHTFYVRTPELDVDSLSAAVRDLQQYHDVFRMRLKREEVGFVQSFAEDFSPAQLRVLNVKDVDGSAAVNEILDGWQSGFNLENGPIGSIGYLHGYEDRSARVWFSVHHMAIDTVSWQILVRDLQTLYRNGSLGSKGSSFRQWAEAIQNYKASDSERNHWNKLVMETASSISALPTSTGSRVRLSRSLSPEKTASLIQGGIDRQDVSVYDSLLTSVGLALQHIAPTGPSMVTIEGHGREEVDQTLDVSRTMGWFTTMYPFEIPRLSTENIVQGVVAVSERFRQVPARGVGYGTLYGYTQHPLPQVTVNYLGQLARKQSKPKEWVLAVGDNEFEYGLMTSPEDKDRSSSAVDVTAVCIDGTMIIDVDSAWSLEESEQFISSIEEGLNKILDGRASQQTSRFPDVPQPAETYTPYFEYLEPPRQGPTLFLLPPGEGGAESYFNNIVKRLRQTNMVVFNNYYLHSKRLRTFEELAEMYLDQVRGIQPHGPYHFIGWSFGGILAMEMSRRLVASDEKIGFLGIIDTYFNVRGATRTIGLGDTEILDPIHHIYNPDPANFQRLPSATDRIVLFKAMRPNNKYESENQRRLYEYYDGTRLNGLDSLLPSDSDVQLVPLTDDTHFSWVGNPQQVEQMCATIKEHLARY

Sequence caution

The sequence AAA63415.1 differs from that shown. Reason: Erroneous gene model prediction

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M57425
EMBL· GenBank· DDBJ
AAA63415.1
EMBL· GenBank· DDBJ
Genomic DNA Sequence problems.
X54296
EMBL· GenBank· DDBJ
CAA38195.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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