ID   UCSC_ACRSP              Reviewed;         492 AA.
AC   A0A411KUP9;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   25-MAY-2022, entry version 9.
DE   RecName: Full=Alpha/beta hydrolase ucsC {ECO:0000303|PubMed:29373009};
DE            EC=3.7.1.- {ECO:0000305|PubMed:29373009};
DE   AltName: Full=UCS1025A pyrrolizidinone biosynthesis cluster protein C {ECO:0000303|PubMed:29373009};
GN   Name=ucsC {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: Alpha/beta hydrolase; 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:0000305|PubMed:29373009}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q93NG6}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. FUS2 hydrolase
CC       family. {ECO:0000305}.
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DR   EMBL; MH375766; QBC88147.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411KUP9; -.
DR   SMR; A0A411KUP9; -.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR000073; AB_hydrolase_1.
DR   Pfam; PF12697; Abhydrolase_6; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Hydrolase.
FT   CHAIN           1..492
FT                   /note="Alpha/beta hydrolase ucsC"
FT                   /id="PRO_0000450532"
FT   ACT_SITE        258
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WZB3"
SQ   SEQUENCE   492 AA;  54716 MW;  FFF21760922AE98A CRC64;
     MYPFFTYSPG RHYFEYKWYN LELLRLIGSA PYGGCDAAEF LELVASLKPN DADEWHHKFL
     ALAERTQAKG EQMSEAGHEA VARGAYLRAS NYFRCAQYMF PIMPAARQGE FLKLYHRSIR
     SFEQAAELME HRVERVSIPF QPPEYRAPAV ELPGWLHLPA AHQRLSGRKT PLLICVGGAD
     STQEELYFLS AAEGPGLGYA ILTFDGPGQG LTLRESGVPL RPDGEVVIEA VLDFIESYAA
     EHPEADLDVD AISITGQSLG GYLALRGAAD PRIKACVAVD PIYDFYDLAM SRMPRWFMWP
     WERNYMGDGF VDFAVIEHSK LDVATKYTFA QGGQMFGSAS PAQMIRDMKQ YTFRLDKTIT
     ASKRHGNNRD YLEWVTCPVF VTGAAGDEKL FLPEMSTSAI MRNLANVPDE HKELWIPKEW
     SEGGAQAKSG AWPLLQHRCF KFLDEKLGIS RGAKPVQLKT GFVKGVNGHG LTNGGLNGAL
     NGATNGITNG VH