UCSF_ACRSP
ID UCSF_ACRSP Reviewed; 333 AA.
AC A0A411KUQ7;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=2-oxoglutarate-dependent dioxygenase ucsF {ECO:0000303|PubMed:29373009};
DE EC=1.14.11.- {ECO:0000269|PubMed:29373009};
DE AltName: Full=UCS1025A pyrrolizidinone biosynthesis cluster protein F {ECO:0000303|PubMed:29373009};
GN Name=ucsF {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, DISRUPTION PHENOTYPE,
RP CATALYTIC ACTIVITY, 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: 2-oxoglutarate-dependent dioxygenase; part of the gene
CC cluster that mediates the biosynthesis of UCS1025A, a member of the
CC pyrrolizidinone family that acts as a strong telomerase inhibitor and
CC displays potent antibacterial and antitumor properties
CC (PubMed:29373009). These compounds share a hemiaminal-containing
CC pyrrolizidinone core fused with a gamma-lactone, giving a
CC furopyrrolizidine that is connected to a decalin fragment
CC (PubMed:29373009). The polyketide synthase module (PKS) of the PKS-NRPS
CC ucsA is responsible for the synthesis of the polyketide backbone via
CC the condensation of an acetyl-CoA starter unit with 6 malonyl-CoA units
CC (PubMed:29373009). The downstream nonribosomal peptide synthetase
CC (NRPS) module then amidates the carboxyl end of the polyketide with a
CC 2S,3S-methylproline derived from L-isoleucine by the 2-oxoglutarate-
CC dependent dioxygenase ucsF which converts L-isoleucine to (4S,5S)-4-
CC methylpyrroline-5-carboxylate that is further converted to 2S,3S-
CC 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 -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:29373009}.
CC -!- DISRUPTION PHENOTYPE: Leads to the complete abolishment of all
CC products. {ECO:0000269|PubMed:29373009}.
CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MH375769; QBC88150.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A411KUQ7; -.
DR SMR; A0A411KUQ7; -.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..333
FT /note="2-oxoglutarate-dependent dioxygenase ucsF"
FT /id="PRO_0000450536"
FT DOMAIN 174..296
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 202
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 204
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 264
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 287
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 333 AA; 37179 MW; 8127A39B4EC0A873 CRC64;
MGVPLLDVSQ LQAGPEARKQ YLQALVQSFR DYGFVRLTKH DVPAKRVQRI FDLSTQMFNL
DIDSKLEFAN IADGSPQRGY SAVGVEKTAS LHGNLIGRRV DEKLTDAREH FDCGSPLDKS
FANRWPEKLQ GFQQELESFY FELEQVTAGI LGSLEEALNC PPGTLNNMIT KENNASELRL
NHYPPVPAGT LRNGNVARIW PHFDLGVITL LFTSAVGGLE VEDRNAPGPQ TFIPVEPETE
AELIVNISET LQRWTDDHLP AGLHRVTIPK DLDTEIQNDA NVEIPGRYSI AYLCKADREA
DVGTLPVFQT GEAPRYKAMT ASEYHRSRLL TAY
