ID   CLAB_PENCR              Reviewed;         214 AA.
AC   A0A481WNL0;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   23-FEB-2022, entry version 4.
DE   RecName: Full=Clavatol biosynthesis cluster protein B {ECO:0000303|PubMed:30811183};
DE   Flags: Precursor;
GN   Name=claB {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: Part of the cla gene cluster that produces clavatol and
CC       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). The function of claB 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}.
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DR   EMBL; MK360918; QBK15040.1; -; Genomic_DNA.
PE   3: Inferred from homology;
KW   Glycoprotein; Signal.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..214
FT                   /note="Clavatol biosynthesis cluster protein B"
FT                   /id="PRO_5019840267"
FT   CARBOHYD        103
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        204
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   214 AA;  24011 MW;  F110540EC369D361 CRC64;
     MAALSFQCLC VASAVRAWER IESMVDVSFD VIIAASAQTI QLSQQSQQCQ LHSQSSAAEA
     YNTFIRIYGR LVPLLERAIT TYATNLQPPL STSPTFQRTD PRNLTYPLDN QVLGSVLRDF
     STHRSLQEQR NPATMVCRPS KMTLGQYEMD EQQSQYLALD VICRTLRNLV IVLQEMGGGE
     NAEIRQVDAR LLTILVQVRR LLENTSATLS ILES