ID   CCSE_ASPCL              Reviewed;         436 AA.
AC   A1CLZ0;
DT   30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 1.
DT   25-MAY-2022, entry version 60.
DE   RecName: Full=Hydrolyase ccsE {ECO:0000303|PubMed:21983160};
DE            EC=3.7.1.- {ECO:0000305|PubMed:21983160};
DE   AltName: Full=Cytochalasin biosynthesis protein E {ECO:0000303|PubMed:21983160};
GN   Name=ccsE {ECO:0000303|PubMed:21983160}; ORFNames=ACLA_078680;
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: Hydrolyase; part of the gene cluster that mediates the
CC       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: Homodimer. {ECO:0000250|UniProtKB:Q93NG6}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. FUS2 hydrolase
CC       family. {ECO:0000305}.
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DR   EMBL; DS027057; EAW09119.1; -; Genomic_DNA.
DR   RefSeq; XP_001270545.1; XM_001270544.1.
DR   AlphaFoldDB; A1CLZ0; -.
DR   SMR; A1CLZ0; -.
DR   ESTHER; aspcl-CCSE; Duf_1100-S.
DR   EnsemblFungi; EAW09119; EAW09119; ACLA_078680.
DR   GeneID; 4702551; -.
DR   KEGG; act:ACLA_078680; -.
DR   VEuPathDB; FungiDB:ACLA_078680; -.
DR   eggNOG; ENOG502QPTG; Eukaryota.
DR   HOGENOM; CLU_034451_0_0_1; -.
DR   OMA; MQEMKRY; -.
DR   OrthoDB; 1133794at2759; -.
DR   Proteomes; UP000006701; Unassembled WGS sequence.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR000073; AB_hydrolase_1.
DR   Pfam; PF12697; Abhydrolase_6; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Hydrolase; Reference proteome.
FT   CHAIN           1..436
FT                   /note="Hydrolyase ccsE"
FT                   /id="PRO_0000438563"
FT   ACT_SITE        249
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WZB3"
SQ   SEQUENCE   436 AA;  48566 MW;  DB4B0DA73B4EFC66 CRC64;
     MHKLFKNAPF FDFEAIRILG TTCYGGADVA EVFEAVDQIK NNDPETWETA WRIQAERAEK
     LAAEALEHGD RDAALAGYLR ASNYTRASGY MYVSRAESSG EALVQDARAL PIAEKVGELF
     RKAIPLMKGS VHTLGIPYEE YALPGYLYLP PPWRRIPGRK IPILVNSGGA DSCQEELFYL
     NPAAGPGQGY AVVTFDGPGQ GIMLRKYGLE MRPDWEAVTG RVIDFLEEYA AENPHLELDL
     NCIAVSGASM GGYYALRAAA DQRVKACVSI DPFYDMWDFG TAHVSPIFIH AWTSGWISGG
     FVDNLMALLS RLSFQLRWEI SVTGTFFGLS SPSQILLHMK KYTLRSTEEE PEGFLSRVIC
     PVLLSGAGKS LYLDVDNHTR QCYDGLVNVA ERNKQLWIPE SEGQGSLQAK MGAFRLCNQR
     TYRFLDECFG IMRKSL