CHEF_CHAGB
ID CHEF_CHAGB Reviewed; 616 AA.
AC P0CU32; Q2HEW2;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 25-MAY-2022, entry version 18.
DE RecName: Full=FAD-linked oxidoreductase cheF {ECO:0000303|PubMed:33622536};
DE EC=1.-.-.- {ECO:0000305|PubMed:23611317};
DE AltName: Full=Chaetoglobosin A biosynthesis cluster protein F {ECO:0000303|PubMed:33622536};
GN Name=cheF {ECO:0000303|PubMed:33622536}; ORFNames=CHGG_01242-2;
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, DISRUPTION PHENOTYPE, AND PATHWAY.
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: FAD-linked oxidoreductase; part of the gene cluster that
CC mediates the biosynthesis of chaetoglobosin A which has a unique
CC inhibitory activity against actin polymerization in mammalian cells
CC (PubMed:23611317, PubMed:33622536). Chaetoglobosin A and its
CC intermediates are involved in the morphological differentiation of
CC C.globosum (PubMed:33622536). The first step of the pathway is the
CC synthesis of prochaetoglobosin I via condensation of one acetyl-CoA, 8
CC malonyl-CoA, and a L-tryptophan molecule by the PKS-NRPS hybrid
CC synthetase cheA, followed by reduction of backbone double bond to
CC install desired geometry by the enoyl reductase cheB (PubMed:23611317).
CC Further multiple oxidation steps performed by the cytochrome P450
CC monooxygenases cheE and cheG, as well as by the FAD-linked
CC oxidoreductase cheF, lead to the formation of chaetoglobosin A
CC (PubMed:23611317). Depending on the order of action of these
CC reductases, distinct intermediates can be identified (PubMed:23611317).
CC Within the pathway, the cytochrome P450 monooxygenase cheE catalyzes a
CC stereospecific epoxidation on prochaetoglobosin I, cytoglobosin D, and
CC chaetoglobosin J intermediates (PubMed:23611317). The FAD-linked
CC oxidoreductase cheF performs dehydrogenation of the C-20 hydroxyl
CC groups in the 20-dihyrochaetoglobosin A and cytoglobosin D
CC intermediates (PubMed:23611317). Finally, the cytochrome P450
CC monooxygenase cheG can catalyze the stereospecific dihydroxylation of
CC prochaetoglobosin I and prochaetoglobosin IV at C-19 and C-20,
CC respectively (PubMed:23611317). The Diels-Alderase cheD may play a role
CC in the post-PKS-NRPS biosynthetic steps catalyzing Diels-Alder
CC cyclization (Probable). {ECO:0000269|PubMed:23611317,
CC ECO:0000269|PubMed:33622536, ECO:0000305|PubMed:33622536}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
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: Impairs the production of chaetoglobosin A but
CC leads to the accumulation of 20-dihydrochaetoglobosin A
CC (PubMed:23611317). {ECO:0000269|PubMed:23611317}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAQ93007.1; Type=Erroneous gene model prediction; Note=The predicted gene CHGG_01242 has been split into 2 genes: CHGG_01242-1 and CHGG_01242-2.; Evidence={ECO:0000269|PubMed:23611317};
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DR EMBL; CH408029; EAQ93007.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001220463.1; XM_001220462.1.
DR AlphaFoldDB; P0CU32; -.
DR SMR; P0CU32; -.
DR EnsemblFungi; EAQ93007; EAQ93007; CHGG_01242.
DR GeneID; 4387648; -.
DR eggNOG; KOG0158; Eukaryota.
DR OrthoDB; 317492at2759; -.
DR Proteomes; UP000001056; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 2.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS00231; F_ACTIN_CAPPING_BETA; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Oxidoreductase; Reference proteome.
FT CHAIN 1..616
FT /note="FAD-linked oxidoreductase cheF"
FT /id="PRO_0000438244"
FT DOMAIN 160..344
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ SEQUENCE 616 AA; 67142 MW; 288673CC78A12EF0 CRC64;
MMEHTAHDRE LPIRPGWDSV VNIAESRSCF SRFQSCFARP QKLVVVIGLC LLLCSPPPGA
QGLPTAADWK TLSNELSGRL HQGVPLARPC FSTYNGQPAA ADEEECAAIR HRYLDAEFRA
NQYAGFYFAQ GDGCISNTTN QCQLDPENLG ASPGSGLPCN QGLVSPWYVD VRSASDVQSA
FRFARRTGTP ISIKASGHDY VNRHTLPGSL GLWTRNLRNM TYHATFRPAG VSGAEPVQAI
TFGSGVNSNE AQAFAGRNNV TLVGPSSATI AIVGGWTLFG GHSVLSPTLG LGVDRVLQIE
LVTPDGALRI CNRQLHADLF WALRGAGAGT YGVVLSMTVR VEPATPVTLA LLSFTPTLEN
QAPFLDLLIN NTPAWSAGGW GGPMTSSSLA LVSLEQDEAA AAQSMRAAAD YVRGENGTVT
IEQFPTYSEF YARYIAVSES YVGIGALPTL RVLPKRLHDQ PQGRAELLAF LSQRARNNQT
PYLFMTPPAR YSTPRDSTSM HPAWRNSYWL AGFQSSYAWN ASVAERREAA REDQTSARDL
TALAPEGAAY PNEASPWHRD WRREFWGDDN YARLEAVKAR YDPAGLLRCW HCVGFDDAWV
HADPAFECMG AFDGLV
