ID IPNS_STRCL Reviewed; 329 AA. AC P10621; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 02-SEP-2026, entry version 115. DE RecName: Full=Isopenicillin N synthase; DE Short=IPNS; DE EC=1.21.3.1; GN Name=pcbC; OS Streptomyces clavuligerus. OC Bacteria; Bacillati; Actinomycetota; Actinomycetes; Kitasatosporales; OC Streptomycetaceae; Streptomyces. OX NCBI_TaxID=1901; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 27064 / DSM 738 / JCM 4710 / NBRC 13307 / NCIMB 12785 / RC NRRL 3585 / VKM Ac-602; RX PubMed=3130293; DOI=10.1016/0378-1119(88)90557-4; RA Leskiw B.K., Aharonowitz Y., Mevarech M., Wolfe S., Vining L.C., RA Westlake D.W.S., Jensen S.E.; RT "Cloning and nucleotide sequence determination of the isopenicillin N RT synthetase gene from Streptomyces clavuligerus."; RL Gene 62:187-196(1988). CC -!- FUNCTION: Removes, in the presence of oxygen, 4 hydrogen atoms from CC delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to form the CC azetidinone and thiazolidine rings of isopenicillin. CC -!- CATALYTIC ACTIVITY: CC Reaction=N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine + O2 CC = isopenicillin N + 2 H2O; Xref=Rhea:RHEA:22428, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:58399, ChEBI:CHEBI:58572; EC=1.21.3.1; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC -!- PATHWAY: Antibiotic biosynthesis; penicillin G biosynthesis; penicillin CC G from L-alpha-aminoadipate and L-cysteine and L-valine: step 2/3. CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M19421; AAA26770.1; -; Genomic_DNA. DR PIR; A29894; A29894. DR RefSeq; WP_003952506.1; NZ_CM000913.1. DR AlphaFoldDB; P10621; -. DR SMR; P10621; -. DR STRING; 1901.BB341_07795; -. DR GeneID; 93729322; -. DR KEGG; sclf:BB341_07795; -. DR eggNOG; COG3491; Bacteria. DR OrthoDB; 21825at2; -. DR BRENDA; 1.21.3.1; 5988. DR UniPathway; UPA00149; UER00240. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0016216; F:isopenicillin-N synthase activity; IEA:UniProtKB-EC. DR Gene3D; 2.60.120.330; B-lactam Antibiotic, Isopenicillin N Synthase, Chain; 1. DR InterPro; IPR026992; DIOX_N. DR InterPro; IPR044861; IPNS-like_FE2OG_OXY. DR InterPro; IPR027443; IPNS-like_sf. DR InterPro; IPR002057; Isopenicillin-N_synth_CS. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase_dom. DR PANTHER; PTHR47990; 2-OXOGLUTARATE (2OG) AND FE(II)-DEPENDENT OXYGENASE SUPERFAMILY PROTEIN-RELATED; 1. DR Pfam; PF03171; 2OG-FeII_Oxy; 1. DR Pfam; PF14226; DIOX_N; 1. DR PRINTS; PR00682; IPNSYNTHASE. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR PROSITE; PS00185; IPNS_1; 1. DR PROSITE; PS00186; IPNS_2; 1. PE 3: Inferred from homology; KW Antibiotic biosynthesis; Iron; Metal-binding; Oxidoreductase; Vitamin C. FT CHAIN 1..329 FT /note="Isopenicillin N synthase" FT /id="PRO_0000219504" FT DOMAIN 180..286 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT BINDING 87 FT /ligand="isopenicillin N" FT /ligand_id="ChEBI:CHEBI:58399" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 87 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 91 FT /ligand="isopenicillin N" FT /ligand_id="ChEBI:CHEBI:58399" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 91 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 183 FT /ligand="isopenicillin N" FT /ligand_id="ChEBI:CHEBI:58399" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 183 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 189 FT /ligand="isopenicillin N" FT /ligand_id="ChEBI:CHEBI:58399" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 189 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 212 FT /ligand="Fe(2+)" FT /ligand_id="ChEBI:CHEBI:29033" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT BINDING 212 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 214 FT /ligand="Fe(2+)" FT /ligand_id="ChEBI:CHEBI:29033" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT BINDING 214 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 268 FT /ligand="Fe(2+)" FT /ligand_id="ChEBI:CHEBI:29033" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT BINDING 277 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT BINDING 279 FT /ligand="isopenicillin N" FT /ligand_id="ChEBI:CHEBI:58399" FT /evidence="ECO:0000250|UniProtKB:P05326" FT BINDING 279 FT /ligand="N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D- FT valine" FT /ligand_id="ChEBI:CHEBI:58572" FT /evidence="ECO:0000250|UniProtKB:P05326" SQ SEQUENCE 329 AA; 36959 MW; 71AA1CCE9514761C CRC64; MPVLMPSAHV PTIDISPLFG TDAAAKKRVA EEIHGACRGS GFFYATNHGV DVQQLQDVVN EFHGAMTDQE KHDLAIHAYN PDNPHVRNGY YKAVPGRKAV ESFCYLNPDF GEDHPMIAAG TPMHEVNLWP DEERHPRFRP FCEGYYRQML KLSTVLMRGL ALALGRPEHF FDAALAEQDS LSSVSLIRYP YLEEYPPVKT GPDGQLLSFE DHLDVSMITV LFQTQVQNLQ VETVDGWRDI PTSENDFLVN CGTYMAHVTN DYFPAPNHRV KFVNAERLSL PFFLNGGHEA VIEPFVPEGA SEEVRNEALS YGDYLQHGLR ALIVKNGQT //