ID   UCSJ_ACRSP              Reviewed;         348 AA.
AC   A0A411KUU5;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Oxidase ucsJ {ECO:0000303|PubMed:29373009};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29373009};
DE   AltName: Full=UCS1025A pyrrolizidinone biosynthesis cluster protein J {ECO:0000303|PubMed:29373009};
GN   Name=ucsJ {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, AND
RP   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: Oxidase; part of the gene cluster that mediates the
CC       biosynthesis of UCS1025A, a member of the pyrrolizidinone family that
CC       acts as a strong telomerase inhibitor and displays potent antibacterial
CC       and antitumor properties (PubMed:29373009). These compounds share a
CC       hemiaminal-containing pyrrolizidinone core fused with a gamma-lactone,
CC       giving a 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   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:29373009}.
CC   -!- DISRUPTION PHENOTYPE: Leads to the accumulation of a shunt product in
CC       which a double bond is introduced between C5 and C6, thereby scrambling
CC       the existing stereochemistry at both positions.
CC       {ECO:0000269|PubMed:29373009}.
CC   -!- SIMILARITY: Belongs to the avfA family. {ECO:0000305}.
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DR   EMBL; MH375773; QBC88154.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411KUU5; -.
DR   SMR; A0A411KUU5; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR   InterPro; IPR016040; NAD(P)-bd_dom.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   Pfam; PF13460; NAD_binding_10; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   Oxidoreductase.
FT   CHAIN           1..348
FT                   /note="Oxidase ucsJ"
FT                   /id="PRO_0000450541"
SQ   SEQUENCE   348 AA;  37406 MW;  1291C33B84810BF6 CRC64;
     MTKKIFATGA TGYIGGDAIY ALLSASPEYE VSCLVRSGAK ATELVARHPS VRIVDGTLDD
     LELLEEAAAN ADIVCNFAHA THEPSVSALA KGLARRQRPG HGYLIHTMGS GTMIYDDVIQ
     RRFGEHSDKV FNDVEGLPEV LAVPDFAKAR GAENAVRDVG VKNPDRVRTA VVCTGSAYGP
     GRGLVEYRTS AIHELVRCTL SRGHALQVGA GKSAWRNVYI RDLSDVFVKL ITHATNDEQD
     SDNTDESVWG GSGGYYFVEN GEHVWGELAR AISDEAVAQG LIQGGDIESI DAAEAASLAP
     MCNFFWGCNA RVEGRRAARG LNWKPVGPPL VKELEVIVQK EAEKLGLS