TRAB_PENCR
ID TRAB_PENCR Reviewed; 509 AA.
AC A0A481WNM6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Cytochrome P450 monooxygenase traB {ECO:0000303|PubMed:30811183};
DE EC=1.-.-.- {ECO:0000305|PubMed:30811183};
DE AltName: Full=Terrestric acid biosynthesis cluster protein B {ECO:0000303|PubMed:30811183};
GN Name=traB {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, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
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: Cytochrome P450 monooxygenase; part of the tra gene cluster
CC that produces terrestric acid (PubMed:30811183). The clavatol
CC biosynthesis cluster cla and the terrestric acid cluster tra are both
CC 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).
CC {ECO:0000250|UniProtKB:A0A0E0RXA7, ECO:0000250|UniProtKB:A0A161CKG1,
CC ECO:0000269|PubMed:30811183, ECO:0000269|PubMed:31860310}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30811183}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC peniphenone D, penilactone D, penilactone A and penilactone B, as well
CC as of crustosic acid and terrestric acid.
CC {ECO:0000269|PubMed:30811183}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK360919; QBK15050.1; -; Genomic_DNA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..509
FT /note="Cytochrome P450 monooxygenase traB"
FT /id="PRO_0000455067"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 453
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 509 AA; 58071 MW; 77B79972F5837DBC CRC64;
MEDFKVKLVE LVSITGGLIV LFIAYTGFRT VYNASFNRLR HIPGPWINSV SMIPYARHML
AGTTVENSVR LHEKYGDVVR ISPNEVSFIS GETAFPDIYG FRTGKLKGHL NMEKDPVWYV
KPSNGSPSLL QANDEDHARG RRVLSHAFSE RAVAAQEPLV QTYVDQLING LKGATAEKEG
EGVVDMVSWY NWTTFDIIAD LMFGEPFGCL QDLSTHKYVA VLLESFKSLR ILYVLAHFPW
LKYFGNLFLD QRQVQKRKDH LSWVSTQVQK RRDRETTRPD FMTLILANNG NKGSKLTDEE
INSNAFLLLN AGSETTATLL SAVTFLLLKN PRVMEKLKQE IREKFASYEE IQLPTLNTMT
YLHAVLLEAL RYFPPAPVGF GRVVNRGGEF ISGHFLPEGC IVSVSQYAAY HSSRNFKDPD
AFVPERWHVP REKEYADDKR SAAQPFSYGP RGCLGRNLAH AELRIILAKM VWSFDLELEE
RSQDWLSRCK VMRLWVKPEL AVKLKKVIR
