ID   TRAE_PENCR              Reviewed;         156 AA.
AC   A0A481WP37;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   23-FEB-2022, entry version 5.
DE   RecName: Full=Terrestric acid biosynthesis cluster protein E {ECO:0000303|PubMed:30811183};
GN   Name=traE {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], FUNCTION, AND DISRUPTION PHENOTYPE.
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 tra gene cluster that produces terrestric acid
CC       (PubMed:30811183). The clavatol biosynthesis cluster cla and the
CC       terrestric acid cluster tra are both involved in the production of
CC       peniphenones and penilactones (PubMed:30811183). The non-reducing PKS
CC       claF is responsible for the formation of clavatol from successive
CC       condensations of 3 malonyl-CoA units, presumably with a simple acetyl-
CC       CoA starter unit, and 2 methylation steps (PubMed:30811183). The
CC       esterase claE probably collaborates with claF by catalyzing the
CC       hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled
CC       intermediates (By similarity). The clavatol oxidase claD then converts
CC       clavatol to hydroxyclavatol (PubMed:30811183). Spontaneous dehydration
CC       of hydroxyclavatol leads to the accumulation of the highly active
CC       ortho-quinone methide (PubMed:30811183, PubMed:31860310). On the other
CC       hand, the PKS-NRPS hybrid traA is involved in the formation of
CC       crustosic acid, with the help of traB and traD (PubMed:30811183). The
CC       polyketide synthase module (PKS) of traA is responsible for the
CC       synthesis of the polyketide backbone via the condensation of an acetyl-
CC       CoA starter unit with 3 malonyl-CoA units (PubMed:30811183). The
CC       downstream nonribosomal peptide synthetase (NRPS) module then amidates
CC       the carboxyl end of the polyketide with L-malic acid (PubMed:30811183).
CC       Because traA lacks a designated enoylreductase (ER) domain, the
CC       required activity is provided the enoyl reductase traG (By similarity).
CC       Crustosic acid undergoes decarboxylation and isomerization to the
CC       terrestric acid, catalyzed by the 2-oxoglutarate-dependent dioxygenase
CC       traH (PubMed:30811183). Both acids are further converted to the 2
CC       gamma-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). TraE
CC       seems not to be involved in the biosynthesis of peniphenones and
CC       penilactones in the conditioons used to study its function
CC       (PubMed:30811183). {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:0000305|PubMed:30811183}.
CC   -!- DISRUPTION PHENOTYPE: Does not result in significant changes in
CC       sencondary metabolites production. {ECO:0000269|PubMed:30811183}.
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; MK360919; QBK15053.1; -; Genomic_DNA.
DR   InterPro; IPR032710; NTF2-like_dom_sf.
DR   InterPro; IPR037401; SnoaL-like.
DR   Pfam; PF13577; SnoaL_4; 1.
DR   SUPFAM; SSF54427; SSF54427; 1.
PE   3: Inferred from homology;
FT   CHAIN           1..156
FT                   /note="Terrestric acid biosynthesis cluster protein E"
FT                   /id="PRO_0000455061"
SQ   SEQUENCE   156 AA;  16838 MW;  316218DD434A0896 CRC64;
     MAAPALPVSL TPALSDRDAI ADALYRGVIA FDTADEVLFK SALTEDAVLV LNGTVMEGYD
     AIYSGCYVNI AKMDTNHFLT NMRVNITEES KAQVSCSALS QHYRGGEGMK PGSDFLLAGG
     LYAVELVKDA GDGLWKIKHW TLKTTWGQGD WAVFGK