FSA3_FUSSF
ID FSA3_FUSSF Reviewed; 353 AA.
AC A0A0E4FKF7;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 24-JUN-2015, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Trans-enoyl reductase fsa3 {ECO:0000303|PubMed:25770422};
DE EC=1.-.-.- {ECO:0000305|PubMed:25770422};
DE AltName: Full=Fusarisetin A biosynthesis protein 3 {ECO:0000303|PubMed:25770422};
GN Name=fsa3 {ECO:0000303|PubMed:25770422};
OS Fusarium sp. (strain FN080326).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=1608308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RX PubMed=25770422; DOI=10.1016/j.bbrc.2015.03.011;
RA Kato N., Nogawa T., Hirota H., Jang J.H., Takahashi S., Ahn J.S., Osada H.;
RT "A new enzyme involved in the control of the stereochemistry in the decalin
RT formation during equisetin biosynthesis.";
RL Biochem. Biophys. Res. Commun. 460:210-215(2015).
RN [2]
RP FUNCTION.
RX PubMed=28401214; DOI=10.1039/c7cc01929g;
RA Li X., Zheng Q., Yin J., Liu W., Gao S.;
RT "Chemo-enzymatic synthesis of equisetin.";
RL Chem. Commun. (Camb.) 53:4695-4697(2017).
RN [3]
RP FUNCTION.
RX PubMed=29972614; DOI=10.1002/anie.201805050;
RA Kato N., Nogawa T., Takita R., Kinugasa K., Kanai M., Uchiyama M.,
RA Osada H., Takahashi S.;
RT "Control of the stereochemical course of [4+2] cycloaddition during trans-
RT decalin formation by Fsa2-family enzymes.";
RL Angew. Chem. Int. Ed. 57:9754-9758(2018).
RN [4]
RP FUNCTION.
RX PubMed=34121297; DOI=10.1002/anie.202106186;
RA Fujiyama K., Kato N., Re S., Kinugasa K., Watanabe K., Takita R.,
RA Nogawa T., Hino T., Osada H., Sugita Y., Takahashi S., Nagano S.;
RT "Molecular basis for two stereoselective Diels-Alderases that produce
RT decalin skeletons*.";
RL Angew. Chem. Int. Ed. 60:22401-22410(2021).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of HIV-1 integrase inhibitor equisetin and of
CC fusarisetin A, both trans-fused decalin-containing tetramic acids
CC showing also antimicrobial activity (PubMed:25770422). The PKS module
CC of fsa1 together with the enoylreductase fsa3 catalyze the formation of
CC the polyketide unit which is then conjugated to L-serine by the
CC condensation domain of the fsa1 NRPS module (PubMed:25770422). Activity
CC of the Dieckmann cyclase domain (RED) results in release of the
CC Dieckmann product intermediate (PubMed:25770422). Diels-Alderase fsa2
CC is involved in endo-selective Diels-Alder cycloaddition to form the
CC decalin ring, leading to the production of N-desmethylequisetin also
CC called trichosetin (PubMed:25770422, PubMed:28401214, PubMed:29972614,
CC PubMed:34121297). Subsequent N-methylation is carried out by fsa4 to
CC give equisetin (PubMed:25770422). The enzymatic gene responsible for
CC the conversion of equisetin to fusarisetin A has not been identified
CC yet and is probably located outside of the fsa cluster
CC (PubMed:28401214). {ECO:0000269|PubMed:25770422,
CC ECO:0000269|PubMed:28401214, ECO:0000269|PubMed:29972614,
CC ECO:0000269|PubMed:34121297}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + ATP + 11 H(+) + L-serine + 7 malonyl-CoA + 8
CC NADPH + 2 S-adenosyl-L-methionine = (5S)-3-[(2E,6R,8E,10E,12E)-2,6-
CC dimethyltetradeca-2,8,10,12-tetraenoyl]-5-(hydroxymethyl)pyrrolidine-
CC 2,4-dione + AMP + 7 CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 2
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67324, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:169938, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000305|PubMed:25770422};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67325;
CC Evidence={ECO:0000305|PubMed:25770422};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:25770422}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- DISRUPTION PHENOTYPE: Results in the loss of production of equisetin
CC and fusarisetin A (PubMed:25770422). {ECO:0000269|PubMed:25770422}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; LC025956; BAR40285.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0E4FKF7; -.
DR SMR; A0A0E4FKF7; -.
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; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
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.
FT CHAIN 1..353
FT /note="Trans-enoyl reductase fsa3"
FT /id="PRO_0000441295"
FT BINDING 45..48
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 131..138
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 166..169
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 189..192
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 207
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 254..255
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 275..279
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 344..345
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 353 AA; 38144 MW; 34B68B09FC50C6BF CRC64;
MVQRQQTALV GTDDGGIRLS STETIPNITG DSVLIKTKAV SVNPVDTKMI GPYVTPGAVA
GFDFAGVVEM VGPDATKCDI RVGDRVCTAI MGMNPLDPTV GAFAEYTAAV EWILLKIPPN
LSFEEGASLG ISFMTTGLAL FKSLGLPGNP LSPATEKLPV LVYGGSSATG TAAIQLVKLA
GFAPITTCSP RNFELVKSYG ASAVFDYNDP DCIRDIKKHT KNNIRYALDC ISTTQSMQFC
YQAIGRAGGK YTALEPFSEA VARTRKMVKP DWIMGPQMLG KEIRWPEPHW RPANAEMGEF
GVYWTAVLRK LLDNNLIRPH AIVVREGGLE KVLDGIEDIR AKKISGKKLV FTL
