ID   CLAE_PENCR              Reviewed;         265 AA.
AC   A0A481WP25;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 6.
DE   RecName: Full=Esterase claE {ECO:0000303|PubMed:30811183};
DE            EC=3.1.2.- {ECO:0000305|PubMed:30811183};
DE   AltName: Full=Terrestric acid biosynthesis cluster protein E {ECO:0000303|PubMed:30811183};
GN   Name=claE {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: Esterase; part of the cla gene cluster that produces clavatol
CC       and ortho-quinone methide (PubMed:30811183). The clavatol biosynthesis
CC       cluster cla and the terrestric acid cluster tra are both involved in
CC       the production of peniphenones and penilactones (PubMed:30811183). The
CC       non-reducing PKS claF is responsible for the formation of clavatol from
CC       successive condensations of 3 malonyl-CoA units, presumably with a
CC       simple acetyl-CoA starter unit, and 2 methylation steps
CC       (PubMed:30811183). The esterase claE probably collaborates with claF by
CC       catalyzing the hydrolysis of ACP-bound acyl intermediates to free the
CC       ACP from stalled intermediates (By similarity). The clavatol oxidase
CC       claD then converts clavatol to hydroxyclavatol (PubMed:30811183).
CC       Spontaneous dehydration of hydroxyclavatol leads to the accumulation of
CC       the highly active ortho-quinone methide (PubMed:30811183,
CC       PubMed:31860310). On the other hand, the PKS-NRPS hybrid traA is
CC       involved in the formation of crustosic acid, with the help of traB and
CC       traD (PubMed:30811183). The polyketide synthase module (PKS) of traA is
CC       responsible for the synthesis of the polyketide backbone via the
CC       condensation of an acetyl-CoA starter unit with 3 malonyl-CoA units
CC       (PubMed:30811183). The downstream nonribosomal peptide synthetase
CC       (NRPS) module then amidates the carboxyl end of the polyketide with L-
CC       malic acid (PubMed:30811183). Because traA lacks a designated
CC       enoylreductase (ER) domain, the required activity is provided the enoyl
CC       reductase traG (By similarity). Crustosic acid undergoes
CC       decarboxylation and isomerization to the terrestric acid, catalyzed by
CC       the 2-oxoglutarate-dependent dioxygenase traH (PubMed:30811183). Both
CC       acids are further converted to the 2 gamma-butyrolactones (R)-5-
CC       methyltetronic acid and (S)-5-carboxylmethyltetronic acid, with
CC       involvement of the cytochrome P450 monooxygenase claJ
CC       (PubMed:30811183). Spontaneous addition of the methide to these gamma-
CC       butyrolactones leads to peniphenone D and penilactone D, which undergo
CC       again stereospecific attacking by methide to give penilactones A and B
CC       (PubMed:30811183, PubMed:31860310). {ECO:0000250|UniProtKB:A0A0E0RXA7,
CC       ECO:0000250|UniProtKB:A0A161CKG1, ECO:0000269|PubMed:30811183,
CC       ECO:0000269|PubMed:31860310}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000250|UniProtKB:A0A161CKG1}.
CC   -!- SIMILARITY: Belongs to the LovG family. {ECO:0000305}.
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DR   EMBL; MK360918; QBK15043.1; -; Genomic_DNA.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR005645; FSH_dom.
DR   Pfam; PF03959; FSH1; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Hydrolase.
FT   CHAIN           1..265
FT                   /note="Esterase claE"
FT                   /id="PRO_0000455064"
FT   ACT_SITE        121
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:A0A161CKG1"
FT   ACT_SITE        211
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P38777"
FT   ACT_SITE        239
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P38777"
SQ   SEQUENCE   265 AA;  30003 MW;  DBD8FA04FC3FB836 CRC64;
     MNTTRTLDNS TIHLPRILCL HGGGTNARIF RAQCRGLIAG LKSEYRLVFA QAPFASQAGS
     DVLSVYSQWG PFRRWLRWRP EHPVIPPEDA VQEIDTWLEK AMHQDDLAGA TGEWIALLGF
     SQGAKVSASL LYRQQSWQEL FGTRPAGINF RFGILLAGQA PFISMDSDLT LDPPLPDASQ
     ITDLKHSERE LFYGKGHVLR IPTLHVHGLR DKGLDHHRKL FEDFCAPQSR RLIEWDGDHR
     VPLKLKDVSL VIHQIRELAK ETGVY