CCSC_ASPCL
ID CCSC_ASPCL Reviewed; 364 AA.
AC A1CLZ2;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Trans-enoyl reductase ccsC {ECO:0000303|PubMed:21983160};
DE EC=1.-.-.- {ECO:0000305|PubMed:21983160, ECO:0000305|PubMed:27551732};
DE AltName: Full=Cytochalasin biosynthesis protein C {ECO:0000303|PubMed:21983160};
GN Name=ccsC {ECO:0000303|PubMed:21983160}; ORFNames=ACLA_078700;
OS Aspergillus clavatus (strain ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 /
OS NRRL 1 / QM 1276 / 107).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=344612;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP FUNCTION, AND PATHWAY.
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=21983160; DOI=10.1016/j.ymben.2011.09.008;
RA Qiao K., Chooi Y.H., Tang Y.;
RT "Identification and engineering of the cytochalasin gene cluster from
RT Aspergillus clavatus NRRL 1.";
RL Metab. Eng. 13:723-732(2011).
RN [3]
RP FUNCTION.
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=24838010; DOI=10.1038/nchembio.1527;
RA Hu Y., Dietrich D., Xu W., Patel A., Thuss J.A., Wang J., Yin W.B.,
RA Qiao K., Houk K.N., Vederas J.C., Tang Y.;
RT "A carbonate-forming Baeyer-Villiger monooxygenase.";
RL Nat. Chem. Biol. 10:552-554(2014).
RN [4]
RP FUNCTION.
RX PubMed=27551732; DOI=10.1371/journal.pone.0161199;
RA Nielsen M.L., Isbrandt T., Petersen L.M., Mortensen U.H., Andersen M.R.,
RA Hoof J.B., Larsen T.O.;
RT "Linker flexibility facilitates module exchange in fungal hybrid PKS-NRPS
RT engineering.";
RL PLoS ONE 11:E0161199-E0161199(2016).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of a family of the mycotoxins cytochalasins E and K
CC (PubMed:21983160). The hybrid PKS-NRPS synthetase ccsA and the enoyl
CC reductase ccsC are responsible for fusion of phenylalanine with an
CC octaketide backbone and subsequent release of the stable tetramic acid
CC precursor (PubMed:21983160, PubMed:27551732). The polyketide synthase
CC module (PKS) of the PKS-NRPS ccsA is responsible for the synthesis of
CC the octaketide backbone (PubMed:21983160). The downstream nonribosomal
CC peptide synthetase (NRPS) amidates the carboxyl end of the octaketide
CC with a phenylalanine (PubMed:21983160). A reductase-like domain (R) at
CC the C-terminus catalyzes the reductive release of the polyketide-amino
CC acid intermediate (PubMed:21983160). Because ccsA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided the enoyl
CC reductase ccsC (PubMed:21983160, PubMed:27551732). Upon formation of
CC the 11-membered carbocycle-fused perhydroisoindolone intermediate, a
CC number of oxidative steps are required to afford the final cytochalasin
CC E and K, including two hydroxylations at C17 and C18, one alcohol
CC oxidation at C17, one epoxidation at C6 and C7 and two Baeyer-Villiger
CC oxidations (PubMed:21983160). The oxidative modification at C17, C18
CC and the C6-C7 epoxidation are likely to be catalyzed by the two
CC cytochrome P450 oxygenases ccsD and ccsG (PubMed:21983160). CcsD may be
CC responsible for the epoxidation of the C6-C7 double bond
CC (PubMed:21983160). CcsG may be responsible for the successive oxidative
CC modifications at C17 and C18 (PubMed:21983160). The double Baeyer-
CC Villiger oxidations of ketocytochalasin to precytochalasin and
CC cytochalasin Z(16) are among the final steps leading to cytochalasin E
CC and K and are catalyzed by ccsB (PubMed:21983160, PubMed:24838010). The
CC first oxygen insertion step follows that of the classic BVMO mechanism,
CC generating the ester precytochalasin (PubMed:24838010). Release of
CC precytochalasin into an aqueous environment can generate the shunt
CC product iso-precytochalasin through spontaneous isomerization
CC (PubMed:24838010). Alternatively, precytochalasin can undergo further
CC oxidation by ccsB to yield the in-line carbonate-containing
CC cytochalasin Z(16) (PubMed:24838010). Cytochalasin Z(16) is a precursor
CC to cytochalasin E and cytochalasin K, whereas iso-precytochalasin is a
CC precursor to cytochalasin Z(17) and rosellichalasin (PubMed:21983160,
CC PubMed:24838010). The hydrolyase ccsE may catalyze hydrolysis of
CC epoxide bond in cytochalasin E to afford cytochalasin K
CC (PubMed:21983160). The function of ccsF has not been assigned but it
CC may play a role in post-PKS-NRPS biosynthetic step, resistance or
CC transport of cytochalasins and related PKS-NRPS products
CC (PubMed:21983160). {ECO:0000269|PubMed:21983160,
CC ECO:0000269|PubMed:24838010, ECO:0000269|PubMed:27551732}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:21983160}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; DS027057; EAW09121.1; -; Genomic_DNA.
DR RefSeq; XP_001270547.1; XM_001270546.1.
DR AlphaFoldDB; A1CLZ2; -.
DR SMR; A1CLZ2; -.
DR STRING; 5057.CADACLAP00007127; -.
DR EnsemblFungi; EAW09121; EAW09121; ACLA_078700.
DR GeneID; 4702655; -.
DR KEGG; act:ACLA_078700; -.
DR VEuPathDB; FungiDB:ACLA_078700; -.
DR eggNOG; KOG1198; Eukaryota.
DR HOGENOM; CLU_026673_16_1_1; -.
DR OMA; CLEMYPD; -.
DR OrthoDB; 727365at2759; -.
DR Proteomes; UP000006701; 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; IPR013149; ADH-like_C.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..364
FT /note="Trans-enoyl reductase ccsC"
FT /id="PRO_0000438565"
FT BINDING 52..55
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 141..148
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 176..179
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 199..202
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 217
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 264..265
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 284..288
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 353..354
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 364 AA; 39702 MW; 4A01C52C50A318DB CRC64;
MTVPTTIRLP SKQTVILEGD DLRLRIDDNA PLPVLRPDEV LVRTMAVAIN PCDYKMHERF
PSPGAVDGCD FSGVILAIGA GVPSLGVSFQ IGDRVCGAVH GSNPIRHDSG SFAEYIASEA
EFTLKIPDSM SFEEAAALGG TGLATLGMAL FRTLELPGTP EEPAQKPLTV LVHGGSSSVG
TMAMQLLRLV GHIPITTCSP RNFALAKEYG AEEIFDYHEP DCGQKIKAYT RNTLRYVLDP
FTDAKSIALC CGAMGRAGGR YACLEMYPDY LVEKRTLRVG FVMGPALLGH RLELDYGYER
AADPEMRQFG IRWYRSIQWL LSKGQLKPHP LRVLPGRFDA ILQGIEMLKS KSVSGEKLVV
SIGM
