BREF2_EUPBR
ID BREF2_EUPBR Reviewed; 308 AA.
AC A0A068ACU9;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Thiohydrolase {ECO:0000303|PubMed:24845309};
DE Short=TH {ECO:0000303|PubMed:24845309};
DE EC=3.1.-.- {ECO:0000269|PubMed:24845309};
DE AltName: Full=Brefeldin A biosynthesis cluster protein Bref-TH {ECO:0000303|PubMed:24845309};
GN Name=Bref-TH {ECO:0000303|PubMed:24845309};
GN Synonyms=orf2 {ECO:0000303|PubMed:24845309};
OS Eupenicillium brefeldianum (Penicillium brefeldianum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=1131482;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, CATALYTIC ACTIVITY,
RP AND PATHWAY.
RC STRAIN=ATCC 58665;
RX PubMed=24845309; DOI=10.1021/cb500284t;
RA Zabala A.O., Chooi Y.H., Choi M.S., Lin H.C., Tang Y.;
RT "Fungal polyketide synthase product chain-length control by partnering
RT thiohydrolase.";
RL ACS Chem. Biol. 9:1576-1586(2014).
CC -!- FUNCTION: Thiohydrolase; part of the gene cluster that mediates the
CC biosynthesis of brefeldin A (BFA), a protein transport inhibitor that
CC shows antiviral, antifungal, and antitumor properties
CC (PubMed:24845309). The proposed biosynthesis of BFA involves formation
CC of an acyclic polyketide chain that is differentially tailored
CC throughout the backbone (PubMed:24845309). The highly reducing
CC polyketide synthase Bref-PKS is proposed to synthesize the precisely
CC reduced octaketide precursor, which could then be directly offloaded by
CC the thiohydrolase enzyme Bref-TH followed by a cytochrome P450
CC monooxygenase-mediated formation of the cyclopentane ring and
CC macrocyclization to afford 7-deoxy BFA. Alternatively, the first ring
CC annulation can also occur on the ACP-tethered intermediate before the
CC thiohydrolase release and lactonization (PubMed:24845309). The C7-
CC hydroxylation by another cytochrome P450 monooxygenase is believed to
CC be the final step in the process to obtain the final structure of BFA
CC (PubMed:24845309). In addition to the HRPKS Bref-PKS and the
CC thiohydrolase Bref-TH, the brefeldin A biosynthesis cluster contains 4
CC cytochrome p450 monooxygenases (called orf3 to orf6), as well a the
CC probable cluster-specific transcription regulator orf8
CC (PubMed:24845309). {ECO:0000269|PubMed:24845309}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:24845309}.
CC -!- INDUCTION: Coexpressed with the other cluster genes on brefeldin A
CC production optimized medium. {ECO:0000269|PubMed:24845309}.
CC -!- SIMILARITY: Belongs to the polyketide transferase af380 family.
CC {ECO:0000305}.
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DR EMBL; KJ728786; AIA58903.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A068ACU9; -.
DR SMR; A0A068ACU9; -.
DR ESTHER; eupbr-bref2; Thiohydrolase.
DR GO; GO:0016787; F:hydrolase 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 1: Evidence at protein level;
KW Hydrolase; Virulence.
FT CHAIN 1..308
FT /note="Thiohydrolase"
FT /id="PRO_0000444930"
SQ SEQUENCE 308 AA; 33884 MW; 76E7C59F570463F8 CRC64;
MPGRELAPRQ NVEFQTLDGL TLRGWLFPAQ SRGPAVIITP GFNCVKEMFV SEVAESFQHS
DVTALVYDPR TLGDSGGLPR NNIDPLAQVS DYSDALTFLK TLPIVDQTNI SFWGMSFSAL
VALNAAALDK RARCCIAVCP LTGMQPEPDM LPKVLARCMQ DRESQVVGNP PVTISVLTEQ
GRNPAGMGIG ADKMEYDYMV NAKFRGAPNY ENRTTLQSYY KMMAWQPFEI MKYLSKTRVL
MIIPENDTIS PADKQQVLFD GLPEPKTAHI AKGKGHLDVL SGADYEILAE MQAYFIKGPR
GKGNAPSA
