ID   CLAC_PENCR              Reviewed;         878 AA.
AC   A0A481WNM8;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 14.
DE   RecName: Full=Enoyl-CoA isomerase/hydratase claC {ECO:0000303|PubMed:30811183};
DE            EC=4.2.1.- {ECO:0000305|PubMed:30811183};
DE   AltName: Full=Clavatol biosynthesis cluster protein C {ECO:0000303|PubMed:30811183};
GN   Name=claC {ECO:0000303|PubMed:30811183};
OS   Penicillium crustosum (Blue mold fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=36656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=PRB-2;
RX   PubMed=30811183; DOI=10.1021/jacs.9b00110;
RA   Fan J., Liao G., Kindinger F., Ludwig-Radtke L., Yin W.B., Li S.M.;
RT   "Peniphenone and penilactone formation in Penicillium crustosum via 1,4-
RT   Michael additions of ortho-quinone methide from hydroxyclavatol to gamma-
RT   butyrolactones from Crustosic Acid.";
RL   J. Am. Chem. Soc. 141:4225-4229(2019).
RN   [2]
RP   FUNCTION.
RX   PubMed=31860310; DOI=10.1021/acs.joc.9b02971;
RA   Liao G., Fan J., Ludwig-Radtke L., Backhaus K., Li S.M.;
RT   "Increasing Structural Diversity of Natural Products by Michael Addition
RT   with ortho-Quinone Methide as the Acceptor.";
RL   J. Org. Chem. 85:1298-1307(2020).
CC   -!- FUNCTION: Enoyl-CoA isomerase/hydratase; part of the cla gene cluster
CC       that produces clavatol and ortho-quinone methide (PubMed:30811183). The
CC       clavatol biosynthesis cluster cla and the terrestric acid cluster tra
CC       are both involved in the production of peniphenones and penilactones
CC       (PubMed:30811183). The non-reducing PKS claF is responsible for the
CC       formation of clavatol from successive condensations of 3 malonyl-CoA
CC       units, presumably with a simple acetyl-CoA starter unit, and 2
CC       methylation steps (PubMed:30811183). The esterase claE probably
CC       collaborates with claF by catalyzing the hydrolysis of ACP-bound acyl
CC       intermediates to free the ACP from stalled intermediates (By
CC       similarity). The clavatol oxidase claD then converts clavatol to
CC       hydroxyclavatol (PubMed:30811183, PubMed:31860310). Spontaneous
CC       dehydration of hydroxyclavatol leads to the accumulation of the highly
CC       active ortho-quinone methide (PubMed:30811183). On the other hand, the
CC       PKS-NRPS hybrid traA is involved in the formation of crustosic acid,
CC       with the help of traB and traD (PubMed:30811183). The polyketide
CC       synthase module (PKS) of traA is responsible for the synthesis of the
CC       polyketide backbone via the condensation of an acetyl-CoA starter unit
CC       with 3 malonyl-CoA units (PubMed:30811183). The downstream nonribosomal
CC       peptide synthetase (NRPS) module then amidates the carboxyl end of the
CC       polyketide with L-malic acid (PubMed:30811183). Because traA lacks a
CC       designated enoylreductase (ER) domain, the required activity is
CC       provided the enoyl reductase traG (By similarity). Crustosic acid
CC       undergoes decarboxylation and isomerization to the terrestric acid,
CC       catalyzed by the 2-oxoglutarate-dependent dioxygenase traH
CC       (PubMed:30811183). Both acids are further converted to the 2 gamma-
CC       butyrolactones (R)-5-methyltetronic acid and (S)-5-
CC       carboxylmethyltetronic acid, with involvement of the cytochrome P450
CC       monooxygenase claJ (PubMed:30811183). Spontaneous addition of the
CC       methide to these gamma-butyrolactones leads to peniphenone D and
CC       penilactone D, which undergo again stereospecific attacking by methide
CC       to give penilactones A and B (PubMed:30811183, PubMed:31860310). The
CC       function of the enoyl-CoA isomerase/hydratase claC has not been
CC       investigated yet (Probable). {ECO:0000250|UniProtKB:A0A0E0RXA7,
CC       ECO:0000250|UniProtKB:A0A161CKG1, ECO:0000269|PubMed:30811183,
CC       ECO:0000269|PubMed:31860310, ECO:0000305|PubMed:30811183}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:30811183}.
CC   -!- SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.
CC       {ECO:0000305}.
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DR   EMBL; MK360918; QBK15041.1; -; Genomic_DNA.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.12.10; -; 1.
DR   Gene3D; 3.30.559.10; -; 2.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR   InterPro; IPR018376; Enoyl-CoA_hyd/isom_CS.
DR   InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR   InterPro; IPR014748; Enoyl-CoA_hydra_C.
DR   Pfam; PF00378; ECH_1; 1.
DR   SUPFAM; SSF52096; SSF52096; 1.
DR   PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE   3: Inferred from homology;
KW   Isomerase; Lyase.
FT   CHAIN           1..878
FT                   /note="Enoyl-CoA isomerase/hydratase claC"
FT                   /id="PRO_0000455065"
FT   REGION          541..561
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        541..556
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         677..681
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P42126"
FT   BINDING         724
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P42126"
FT   SITE            747
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P42126"
SQ   SEQUENCE   878 AA;  94668 MW;  919A5834C7DFB32E CRC64;
     MERSFTVECP PFEVEISHWD RILPPTHSKR ILCFSLPETT DKEKVVEQLH IAFHHTVQRL
     PLLAGSVVPF SSHQGGRPWL RNIIPEGGAQ LIVKDLSEEL RFSDLAKTNF SQHLLNTEQL
     CPLPEVGYFK NESVDVCRFQ ANFIEGGLLL VVSIIHNAAD GRGVTEVIKI FANELSKAQS
     GETHYPLEPR PDVYRTDRTK LVSGHGVPGS IENHAAWTSD PANAHAQIHN VENSCRTFRI
     SVKALSDLKK SLSATSRGPD EWFSTNDAIS AFIWRSIMLA RHRAGILNGD AETYVAQPVD
     CRPHLEIPMP YFGNVIYMTK SSVPLSDLAD FESGLGAAAR ALRADIKGVT AEKFRDLVGY
     AERTALETHT RLNILEAMST SGIILTSLFK MDLHGMNFGP IFGDGHIKAL RLPARGTQAG
     AVIVLPRVPD GSCEFMVTEQ ESTIKCLLED EYFSRFTNDA DSIGASSEEV VAPLPQPPIT
     SEEGMISIDS TPPVIEAITI KSAPDIEPVT IEAATTEVEP ITIKSISDTE TVTIGITTTE
     VGPASTEATS PVVEPSTMES DLVEPVTVGT TNSEVESVTT ETTASKVQAL TTISKEWHLV
     PAGDVKMPST LISNRIDAPQ VGTIKIIQLN RPAAKNALSV QMVHELSCEI EEIHNERHMG
     GTRALVIASA VDGVFCAGAD LKERKDMSLT ETQAFLTSLR GLYSRLAALP IPTIACVSGH
     ALGGGLELAL CCHLRVFASN AVAALPETRL AIIPGAGGTY RLPNIVGMSN ALDMILTGRG
     VPASEAAKMG LCNRLVGADG SEDTQAFSNR VLALETGIQL AEQISDAGPI AIRAAIRALS
     YSCEAVENAA YESVLTTKDR KAALAAFSEK RKPILVGE