CHEB_CHAGB
ID CHEB_CHAGB Reviewed; 377 AA.
AC Q2HEW4;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Enoyl reductase cheB {ECO:0000303|PubMed:33622536};
DE EC=1.-.-.- {ECO:0000305|PubMed:23611317};
DE AltName: Full=Chaetoglobosin A biosynthesis cluster protein B {ECO:0000303|PubMed:33622536};
GN Name=cheB {ECO:0000303|PubMed:33622536}; ORFNames=CHGG_01240;
OS Chaetomium globosum (strain ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 /
OS NRRL 1970) (Soil fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=306901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 / NRRL 1970;
RX PubMed=25720678; DOI=10.1128/genomea.00021-15;
RA Cuomo C.A., Untereiner W.A., Ma L.-J., Grabherr M., Birren B.W.;
RT "Draft genome sequence of the cellulolytic fungus Chaetomium globosum.";
RL Genome Announc. 3:E0002115-E0002115(2015).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23611317; DOI=10.1021/ja402828w;
RA Ishiuchi K., Nakazawa T., Yagishita F., Mino T., Noguchi H., Hotta K.,
RA Watanabe K.;
RT "Combinatorial generation of complexity by redox enzymes in the
RT chaetoglobosin A biosynthesis.";
RL J. Am. Chem. Soc. 135:7371-7377(2013).
RN [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=33622536; DOI=10.1016/j.funbio.2020.10.010;
RA Cheng M., Zhao S., Liu H., Liu Y., Lin C., Song J., Thawai C.,
RA Charoensettasilp S., Yang Q.;
RT "Functional analysis of a chaetoglobosin A biosynthetic regulator in
RT Chaetomium globosum.";
RL Fungal Biol. 125:201-210(2021).
CC -!- FUNCTION: Enoyl reductase; part of the gene cluster that mediates the
CC biosynthesis of chaetoglobosin A which has a unique inhibitory activity
CC against actin polymerization in mammalian cells (PubMed:23611317,
CC PubMed:33622536). Chaetoglobosin A and its intermediates are involved
CC in the morphological differentiation of C.globosum (PubMed:33622536).
CC The first step of the pathway is the synthesis of prochaetoglobosin I
CC via condensation of one acetyl-CoA, 8 malonyl-CoA, and a L-tryptophan
CC molecule by the PKS-NRPS hybrid synthetase cheA, followed by reduction
CC of backbone double bond to install desired geometry by the enoyl
CC reductase cheB (PubMed:23611317). Further multiple oxidation steps
CC performed by the cytochrome P450 monooxygenases cheE and cheG, as well
CC as by the FAD-linked oxidoreductase cheF, lead to the formation of
CC chaetoglobosin A (PubMed:23611317). Depending on the order of action of
CC these reductases, distinct intermediates can be identified
CC (PubMed:23611317). Within the pathway, the cytochrome P450
CC monooxygenase cheE catalyzes a stereospecific epoxidation on
CC prochaetoglobosin I, cytoglobosin D, and chaetoglobosin J intermediates
CC (PubMed:23611317). The FAD-linked oxidoreductase cheF performs
CC dehydrogenation of the C-20 hydroxyl groups in the 20-
CC dihyrochaetoglobosin A and cytoglobosin D intermediates
CC (PubMed:23611317). Finally, the cytochrome P450 monooxygenase cheG can
CC catalyze the stereospecific dihydroxylation of prochaetoglobosin I and
CC prochaetoglobosin IV at C-19 and C-20, respectively (PubMed:23611317).
CC The Diels-Alderase cheD may play a role in the post-PKS-NRPS
CC biosynthetic steps catalyzing Diels-Alder cyclization (Probable).
CC {ECO:0000269|PubMed:23611317, ECO:0000269|PubMed:33622536,
CC ECO:0000305|PubMed:33622536}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:23611317}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor cheR that binds directly to an asymmetric direct
CC repeat present in the promoter. {ECO:0000269|PubMed:33622536}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of chaetoglobosin A and
CC 20-dihyrochaetoglobosin A (PubMed:23611317).
CC {ECO:0000269|PubMed:23611317}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; CH408029; EAQ93005.1; -; Genomic_DNA.
DR RefSeq; XP_001220461.1; XM_001220460.1.
DR AlphaFoldDB; Q2HEW4; -.
DR SMR; Q2HEW4; -.
DR STRING; 38033.XP_001220461.1; -.
DR EnsemblFungi; EAQ93005; EAQ93005; CHGG_01240.
DR GeneID; 4387646; -.
DR eggNOG; KOG1198; Eukaryota.
DR HOGENOM; CLU_026673_16_1_1; -.
DR InParanoid; Q2HEW4; -.
DR OMA; CAQDIRA; -.
DR OrthoDB; 727365at2759; -.
DR BioCyc; MetaCyc:MON-19095; -.
DR Proteomes; UP000001056; Unassembled WGS sequence.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..377
FT /note="Enoyl reductase cheB"
FT /id="PRO_0000438242"
FT REGION 18..361
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255"
FT BINDING 49..52
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 137..144
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 173..176
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 200..203
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 218
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 265..266
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 283
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 285..289
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 354..355
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 377 AA; 40831 MW; 5CFA3E6D5F7177D1 CRC64;
MGSFEIPEKH TALLQGEGGS LVIARDVPLP TLGPGHLLVK TAAVALNPCD FKTPAAFPNP
GYYNGCDFAG TVVALGSDNI RDGGPWKIGD RIFGAIHGAN PSDWDSGSHA EYVKAVSVFS
YRIPDWMTFE EAAGLSPCCI ATMGVSLFKA LELPGTFEEP ATKPLDVLIY GGSSSVGSLG
IQMVKLTGHR LGHRCITTCS PKNFDLVKSY GADEVFDYKS PTCAQDIRKA TRNCLKYAVD
PFGEVKTMAI CTEAIGRAGG RYSALEKFQE DVCDRKTVKR ELTMGAIIIG HGLDLGGRYT
RPHSPEMRAW GIEWYKSIQR LVDARKFKPH PIRVLKGGFE DMLEGLAMLK RREISAEKLV
VSLDPAVSGL TADSTAR
