ID   EFUA_HORCR              Reviewed;        1314 AA.
AC   A0A2Z4HPY4;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 1.
DT   03-AUG-2022, entry version 16.
DE   RecName: Full=Enfumafungin synthase efuA {ECO:0000303|PubMed:30051576};
DE   AltName: Full=Enfumafungin biosynthesis cluster protein A {ECO:0000303|PubMed:30051576};
DE   AltName: Full=Terpene cyclase-glycosyl transferase fusion protein efuA {ECO:0000303|PubMed:30051576};
DE   Includes:
DE     RecName: Full=Terpene cyclase {ECO:0000303|PubMed:30051576};
DE              EC=5.4.99.- {ECO:0000305|PubMed:30051576};
DE   Includes:
DE     RecName: Full=Glycosyl transferase {ECO:0000303|PubMed:30051576};
DE              EC=2.4.1.- {ECO:0000305|PubMed:30051576};
GN   Name=efuA {ECO:0000303|PubMed:30051576};
OS   Hormonema carpetanum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Dothideomycetidae; Dothideales; Dothioraceae; Hormonema.
OX   NCBI_TaxID=284138;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP   PATHWAY.
RX   PubMed=30051576; DOI=10.1111/1462-2920.14333;
RA   Kuhnert E., Li Y., Lan N., Yue Q., Chen L., Cox R.J., An Z., Yokoyama K.,
RA   Bills G.F.;
RT   "Enfumafungin synthase represents a novel lineage of fungal triterpene
RT   cyclases.";
RL   Environ. Microbiol. 20:3325-3342(2018).
CC   -!- FUNCTION: Terpene cyclase-glycosyl transferase fusion protein; part of
CC       the gene cluster that mediates the biosynthesis of enfumafungin, a
CC       glycosylated fernene-type triterpenoid with potent antifungal activity,
CC       mediated by its interaction with beta-1,3-glucan synthase and the
CC       fungal cell wall (PubMed:30051576). The pathway begins with the terpene
CC       cyclase-glycosyl transferase fusion protein that most likely uses 2,3-
CC       oxidosqualene as substrate and catalyzes glycosylation immediately
CC       after cyclization (Probable). The fernene glycoside then could be
CC       processed by the desaturase efuI which catalyzes isomerization of a
CC       double bond established by efuA to form the core structure (Probable).
CC       The latter would then undergo a series of hydroxylations in unknown
CC       order at C-2, C-19, C-23 and C-25, which would be catalyzed by two of
CC       the three cytochrome P450 monooxygenases efuB, efuG or efuH (Probable).
CC       The hydroxy-group at C-25 becomes oxidized by the dehydrogenase efuE to
CC       enable a spontaneous, non-enzymatic hemiacetal formation with C-23
CC       (Probable). After hydroxylation at C-2, acetylation by the
CC       acetyltransferase efuC takes place (Probable). The final steps in
CC       enfumafungin biosynthesis require expansion of the 5-membered ring by
CC       lactonization via a Baeyer-Villiger reaction mediated by one of the
CC       BGC's cytochrome P450 monooxygenases (efuB, efuG or efuH) followed by
CC       ring cleavage (Probable). This type of reaction would establish a
CC       double bond between C-20 and C-21 which could be reduced by the
CC       reductase efuL to form the final product (Probable).
CC       {ECO:0000269|PubMed:30051576, ECO:0000305|PubMed:30051576}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:30051576}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of enfumafungin and
CC       loses antifungal activity. {ECO:0000269|PubMed:30051576}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the terpene
CC       cyclase/mutase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the
CC       glycosyltransferase 28 family. {ECO:0000305}.
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DR   EMBL; MF611888; AWW17216.1; -; Genomic_DNA.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005811; C:lipid droplet; IEA:InterPro.
DR   GO; GO:0016758; F:hexosyltransferase activity; IEA:InterPro.
DR   GO; GO:0016866; F:intramolecular transferase activity; IEA:InterPro.
DR   GO; GO:0008194; F:UDP-glycosyltransferase activity; IEA:InterPro.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0030259; P:lipid glycosylation; IEA:InterPro.
DR   GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro.
DR   CDD; cd03784; GT1_Gtf-like; 1.
DR   InterPro; IPR004276; GlycoTrans_28_N.
DR   InterPro; IPR006400; Hopene-cyclase.
DR   InterPro; IPR032696; SQ_cyclase_C.
DR   InterPro; IPR032697; SQ_cyclase_N.
DR   InterPro; IPR018333; Squalene_cyclase.
DR   InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR   InterPro; IPR002213; UDP_glucos_trans.
DR   PANTHER; PTHR11764; PTHR11764; 1.
DR   Pfam; PF03033; Glyco_transf_28; 1.
DR   Pfam; PF13243; SQHop_cyclase_C; 1.
DR   Pfam; PF13249; SQHop_cyclase_N; 1.
DR   Pfam; PF00201; UDPGT; 1.
DR   SFLD; SFLDG01016; Prenyltransferase_Like_2; 1.
DR   SUPFAM; SSF48239; SSF48239; 2.
DR   TIGRFAMs; TIGR01507; hopene_cyclase; 1.
DR   TIGRFAMs; TIGR01787; squalene_cyclas; 1.
PE   3: Inferred from homology;
KW   Isomerase; Membrane; Repeat; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..1314
FT                   /note="Enfumafungin synthase efuA"
FT                   /id="PRO_0000454456"
FT   TRANSMEM        133..153
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        155..175
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        230..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1200..1220
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REPEAT          19..62
FT                   /note="PFTB 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          66..107
FT                   /note="PFTB 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          260..300
FT                   /note="PFTB 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          417..458
FT                   /note="PFTB 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          546..597
FT                   /note="PFTB 5"
FT                   /evidence="ECO:0000255"
FT   REGION          1..680
FT                   /note="Terpenne cyclase"
FT                   /evidence="ECO:0000303|PubMed:30051576"
FT   REGION          681..1314
FT                   /note="Glycosyltransferase"
FT                   /evidence="ECO:0000303|PubMed:30051576"
FT   REGION          1289..1314
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        395
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   SITE            331
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   SITE            384
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   SITE            517
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
SQ   SEQUENCE   1314 AA;  146756 MW;  04B97C4E8167F0F8 CRC64;
     MPSYHNTDKT LLGDARQSLQ QAVDYSLGCQ QPDGHWVAPV MADATFTAQY VFFKHQIPEL
     SLDEDGPEIQ RWLLGEQTAD GSWTLAPDLP GNLSTTVEAY LALRILGVPK SDQAMLRARD
     FVVRNGGVEG VRFFTRFFLA TFGLVPWTAI PQMPAELILL PTFMFLNIYV LSSWARSTLI
     PILLVRHHEP VYALPNGQSA NNNFLDELWC NPGEKNIPFA LPLWDLLRRY QWIEFAFTLL
     DHILALFGGL RRWPCRHMAL KRCTAWLLEH QEESGDWAGF FPPIHGSIWA LLLDGFSFQS
     EVIRLGMEAL ERLVVIDPKG KWVQSTVSPC WDTALMANAL CDAGMSGDTR LAKATQWLRD
     RQLMVSHGDW RNYANTQQAG GWSFQYFNSF YPDVDDTAVV IMTLIKEDPN CTNSDCVMNG
     VEWMLGMQSR DGGWGAFDVN NNARWLHKIP FSDMDSLVDP STSDVTGRIL ECLGLLLSQR
     KSPLSPRWRH RLQASSAKAI AFLAKEQESS GAWWGRWGNN YHYGTANVLR GLAWFAQTDP
     SAQMMCMRTL SWIDETQNAD GGWGETLASY VDKSLAGLGR STAAHTAWAL ESLLRFRLPS
     DQAIERGVRW LIDNQQPNVD GYYYGTKWQA GAGQGASWRF DHAYVGTGFP SVLYLGYPYY
     HHLFPIQALS RYIDKASRQG IETLRIPSSS AVILDRPNVL LMAMGSRGDI QVFLNVTKRL
     SSCRVRIATH PAHQAKVEGH GFEFYDVGGS PEVFSAALAN GHGILRSIID GRFRELQHLL
     RSIYRSFWVA ALDDVQSHSP LKPESSSRPF IADVVVSGPS TSVHVHAAER AQAPLVIIST
     QPAIITGDFQ SPLTMSRAQF NPSRLWNRIS FHMLAFFDWL SFGPSFNRMR ANSYQLRSLD
     LAWALFEFVK VSVPHVCLWS TSLAPKPEDW DNNVIIAGYS SMSDDADDVA SKSLQAFLET
     RQPVVAISFG SATIEDPMKL IKLMSAALVK VGASSVVCRS WDSSFEAEAD LPSNVFLVDS
     IPHGWLLQHV EGFVHHGGAG HTAAGAKAGV SQLVMPQFLD QFFWATKVSE MGLGPTPLPL
     RELFLDELAP RMEDLLSSKY TKACTNMALQ LRGDVDGADV AGDEILRQVE AITTCCIFPE
     LSAHWYCTES DLSLSGAAAA SLVSSKEIQW QDLELRPAKD WEQQWRTVRS SSNLVRIWRA
     IVQLLYGFTT TILALFGWLK GTHGYLDGDR HLIKMEDPLR QARLEQAQFD LHLIHQACDS
     GSSTSLDAKI IENWKARKAV VIHEVFDDDS GASESSRSSL DGGHADSVLD IEEK