UCSL_ACRSP
ID UCSL_ACRSP Reviewed; 400 AA.
AC A0A411KUQ4;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Trans-enoyl reductase ucsL {ECO:0000303|PubMed:29373009};
DE EC=1.-.-.- {ECO:0000269|PubMed:29373009};
DE AltName: Full=UCS1025A pyrrolizidinone biosynthesis cluster protein L {ECO:0000303|PubMed:29373009};
GN Name=ucsL {ECO:0000303|PubMed:29373009};
OS Acremonium sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreales incertae sedis; Acremonium;
OC unclassified Acremonium.
OX NCBI_TaxID=2046025;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=KY4917;
RX PubMed=29373009; DOI=10.1021/jacs.8b00056;
RA Li L., Tang M.C., Tang S., Gao S., Soliman S., Hang L., Xu W., Ye T.,
RA Watanabe K., Tang Y.;
RT "Genome mining and assembly-line biosynthesis of the UCS1025A
RT pyrrolizidinone family of fungal alkaloids.";
RL J. Am. Chem. Soc. 140:2067-2071(2018).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of UCS1025A, a member of the pyrrolizidinone family
CC that acts as a strong telomerase inhibitor and displays potent
CC antibacterial and antitumor properties (PubMed:29373009). These
CC compounds share a hemiaminal-containing pyrrolizidinone core fused with
CC a gamma-lactone, giving a furopyrrolizidine that is connected to a
CC decalin fragment (PubMed:29373009). The polyketide synthase module
CC (PKS) of the PKS-NRPS ucsA is responsible for the synthesis of the
CC polyketide backbone via the condensation of an acetyl-CoA starter unit
CC with 6 malonyl-CoA units (PubMed:29373009). The downstream nonribosomal
CC peptide synthetase (NRPS) module then amidates the carboxyl end of the
CC polyketide with a 2S,3S-methylproline derived from L-isoleucine by the
CC 2-oxoglutarate-dependent dioxygenase ucsF which converts L-isoleucine
CC to (4S,5S)-4-methylpyrroline-5-carboxylate that is further converted to
CC 2S,3S-methylproline by the pyrroline-5-carboxylate reductase ucsG
CC (PubMed:29373009). Reductive release of the completed aminoacyl
CC polyketide from the assembly line can form the 3-pyrrolin-2-one
CC structure via an intramolecular Knoevenagel reaction (PubMed:29373009).
CC Because ucsA lacks a designated enoylreductase (ER) domain, the
CC required activity is provided the enoyl reductase ucsL
CC (PubMed:29373009). This keto acyclic precursor is the substrate of the
CC Diels-Alderase ucsH, that catalyzes the Diels-Alder cycloaddition
CC (PubMed:29373009). Oxidation of the 3S-methyl group to a carboxylate by
CC the cytochrome P450 monooxygenase ucsK allows an oxa-Michael
CC cyclization that might involve the reductase/dehydrogenase ucsI and
CC which furnishes the furopyrrolizidine (PubMed:29373009). The oxidase
CC ucsJ likely plays a critical role in stereoselective reduction of the
CC C5-C6 double bond to afford the required R-configured carboxylate group
CC (Probable). Further enolization and oxidation at C5 by an unidentified
CC enzyme affords the last intermediate that can undergo oxa-Michael
CC cyclization to yield UCS1025A (Probable). {ECO:0000269|PubMed:29373009,
CC ECO:0000305|PubMed:29373009}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:29373009}.
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; MH375775; QBC88156.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A411KUQ4; -.
DR SMR; A0A411KUQ4; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
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..400
FT /note="Trans-enoyl reductase ucsL"
FT /id="PRO_0000450540"
FT BINDING 50..53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 145..152
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 204..207
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 227..230
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 245
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 292..293
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 313..317
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 389..390
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 400 AA; 42535 MW; F20B66AA3BE7FEDF CRC64;
MGSLIQTPST QTAVVTTAEG RHQVAHGRRV PSCGPRSVLV RIKAVALNAT DHKMPARVKR
EGLTSGCDFA GEVVAVGEQA NDEPRRCELP RSWAPGDRVF GVVYGSNPGQ PEWGAFAEYV
EADPIMLCHV PDGWDWETAA SVGGSVHGSV ALCLFGDGNL ALDYSNLKAQ ADSSSADAVT
NQSPKPESFT KEELRKVVLV YGGSTACGTM ALQLLRLAGY TPITTCSPRN FGLVESYGAV
AAFDYHSETC ATEMKTYTRS SLVAALDCLG NTQSAALCYA ALGRAGGRYV ALEKYPDSVS
ATRKLVKPSW VMGPVMFGRE LQLADGYSQP ADLAARAFAC DWYPLAERLV HQERLRAHPV
TIAGPSPPVG DKWADAILCG LQELRDGSVS ASKLVVPVAA
