ID   CLAH_PENCR              Reviewed;         308 AA.
AC   A0A481WQ01;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=Polyketide transferase claH {ECO:0000303|PubMed:30811183};
DE            EC=2.3.-.- {ECO:0000305|PubMed:30811183};
DE   AltName: Full=Clavatol biosynthesis cluster protein H {ECO:0000303|PubMed:30811183};
GN   Name=claH {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: Polyketide transferase; part of the cla gene cluster that
CC       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). Spontaneous dehydration of
CC       hydroxyclavatol leads to the accumulation of the highly active ortho-
CC       quinone methide (PubMed:30811183, PubMed:31860310). On the other hand,
CC       the PKS-NRPS hybrid traA is involved in the formation of crustosic
CC       acid, 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 polyketide transferase claH has not been investigated
CC       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 polyketide transferase af380 family.
CC       {ECO:0000305}.
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DR   EMBL; MK360918; QBK15046.1; -; Genomic_DNA.
DR   GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR022742; Hydrolase_4.
DR   Pfam; PF12146; Hydrolase_4; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Transferase.
FT   CHAIN           1..308
FT                   /note="Polyketide transferase claH"
FT                   /id="PRO_0000455060"
FT   REGION          50..280
FT                   /note="Abhydrolase domain"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   308 AA;  33966 MW;  CD733CA69891B802 CRC64;
     MPNYEKVEFQ TLDGLTLRGR LFRAEGAGGN RTAAVVITPP YVIVQDVMVS DIAVYFSQQG
     ITALTYDTRS FGESDGQPRC ELDLSKQVDD YSDAFTFLAS LPSVDPSKIG FWGISFCATV
     ALNAAALDRR SRFVISVGPI VKASDENPYP IDKVHRVLTK ALRDRESQLR GNTPFYVEST
     CEDGSNPTGF GPELGIEAYE LVQRIAASGI APNFSTQLTL QSFAKILRWH PMQDIKWLGE
     TPMMLMIPGD DTVSLPEEQM RLFDMITGPK RVEVAAGKSH FNVLASEGFE GLMDMQVEFI
     KQTLGLSS