TASC_HAPIR
ID TASC_HAPIR Reviewed; 385 AA.
AC A0A0F7GFI5;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Trans-enoyl reductase tasC {ECO:0000303|PubMed:25885659};
DE Short=ER tasC {ECO:0000303|PubMed:25885659};
DE EC=1.-.-.- {ECO:0000269|PubMed:25885659};
DE AltName: Full=Tetramic acid Sch210971/2 biosynthesis cluster protein C {ECO:0000303|PubMed:25885659};
GN Name=tasC {ECO:0000303|PubMed:25885659};
OS Hapsidospora irregularis.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreales incertae sedis; Hapsidospora.
OX NCBI_TaxID=95324;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=25885659; DOI=10.1021/acs.orglett.5b00715;
RA Kakule T.B., Zhang S., Zhan J., Schmidt E.W.;
RT "Biosynthesis of the tetramic acids Sch210971 and Sch210972.";
RL Org. Lett. 17:2295-2297(2015).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of the tetramic acids Sch210971 and Sch210972,
CC potential anti-HIV fungal natural product that contain a decalin core
CC (PubMed:25885659). The PKS module of tasS together with the
CC enoylreductase tasC catalyze the formation of the polyketide unit which
CC is then conjugated to 4-hydroxyl-4-methyl glutamate (HMG) by the
CC condensation domain of the tasS NRPS module (PubMed:25885659). One
CC unique structural feature of Sch210971 and Sch210972 is the tetramic
CC acid motif proposed to be derived from the non-proteinogenic amino acid
CC HMG, by a Dieckmann-type condensation catalyzed by the reductase domain
CC of tasS (PubMed:25885659). The aldolase tasA catalyzes the aldol
CC condensation of 2 molecules of pyruvic acid to yield the intermediate
CC 4-hydroxyl-4-methyl-2-oxoglutarate (HMOG), which can then be
CC stereoselectively transaminated, may be by tasG, to form HMG
CC (PubMed:25885659). The Diels-Alderase tas3 then uses the Dieckmann
CC product of tasS as substrate and catalyzes the Diels-Alder
CC cycloaddition to form the decalin ring of Sch210971 and Sch210972
CC (PubMed:25885659). {ECO:0000269|PubMed:25885659}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,4S)-4-hydroxy-4-methylglutamate + ATP + 11 H(+) + 8
CC malonyl-CoA + 8 NADPH + 3 S-adenosyl-L-methionine = (2S)-3-[(2S)-3,5-
CC dioxo-4-[(2E,4R,6R,8E,10E,12E)-4,6,12-trimethyltetradeca-2,8,10,12-
CC tetraenoyl]pyrrolidin-2-yl]-2-hydroxy-2-methylpropanoate + AMP + 8
CC CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67264, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:167901, ChEBI:CHEBI:167907,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:25885659};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67265;
CC Evidence={ECO:0000269|PubMed:25885659};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,4R)-4-hydroxy-4-methylglutamate + ATP + 11 H(+) + 8
CC malonyl-CoA + 8 NADPH + 3 S-adenosyl-L-methionine = (2R)-3-[(2S)-3,5-
CC dioxo-4-[(2E,4R,6R,8E,10E,12E)-4,6,12-trimethyltetradeca-2,8,10,12-
CC tetraenoyl]pyrrolidin-2-yl]-2-hydroxy-2-methylpropanoate + AMP + 8
CC CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:167910, ChEBI:CHEBI:167912,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:25885659};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67317;
CC Evidence={ECO:0000269|PubMed:25885659};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25885659}.
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; KP835202; AKG54856.1; -; Genomic_DNA.
DR SMR; A0A0F7GFI5; -.
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 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..385
FT /note="Trans-enoyl reductase tasC"
FT /id="PRO_0000453336"
FT BINDING 49..52
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 136..143
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 196..199
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 219..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 284..285
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 305..309
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 374..375
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 385 AA; 40464 MW; 71547B2D68A6B5B5 CRC64;
MTVSNKTQTA LVGSPDGAII LSDTAPLPPS QLEDEQVAVA VQAVSLNPVD TKMAGDYHTP
GAISGCEFAG VVTAVGPGAA SEWGLGPGDR VSAAIMGMNP LRPSIGAFAQ HSVAPAHCLL
KMRDDWGFAQ AAGLGNSWYT VAWALFHVMG LPAGPELEPL HTKHPPPARE PRISIDNPAP
NGGGGKRTTV LVSGGSSSTG TCAIQLLKLA GFDVVATSSA RNFDLVRSYG ADAVFDHSSP
SVAADIKAHT RNGLRLALDC ITTPDTTRLC YGAIGRTGGR YVSLDPYSEV VAASRAVVRA
DWVLGPELMG EDVGWPAPHG RKGNPEAKAF CKVWNRTLQG LLDRGAIRTH PQRVRDTGLR
GVLEGLDDIR EKRVSGEKLV YTLQV
