ID   UCSG_ACRSP              Reviewed;         318 AA.
AC   A0A411KUQ8;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   25-MAY-2022, entry version 10.
DE   RecName: Full=Pyrroline-5-carboxylate reductase ucsG {ECO:0000303|PubMed:29373009};
DE            EC=1.5.1.- {ECO:0000269|PubMed:29373009};
DE   AltName: Full=UCS1025A pyrrolizidinone biosynthesis cluster protein G {ECO:0000303|PubMed:29373009};
GN   Name=ucsG {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 {ECO:0000312|EMBL:QBC88151.1};
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: Pyrroline-5-carboxylate reductase; part of the gene cluster
CC       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   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:29373009}.
CC   -!- SIMILARITY: Belongs to the pyrroline-5-carboxylate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; MH375770; QBC88151.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411KUQ8; -.
DR   SMR; A0A411KUQ8; -.
DR   GO; GO:0004735; F:pyrroline-5-carboxylate reductase activity; IEA:InterPro.
DR   GO; GO:0006561; P:proline biosynthetic process; IEA:UniProtKB-KW.
DR   HAMAP; MF_01925; P5C_reductase; 1.
DR   InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR028939; P5C_Rdtase_cat_N.
DR   InterPro; IPR029036; P5CR_dimer.
DR   InterPro; IPR000304; Pyrroline-COOH_reductase.
DR   PANTHER; PTHR11645; PTHR11645; 1.
DR   Pfam; PF03807; F420_oxidored; 1.
DR   Pfam; PF14748; P5CR_dimer; 1.
DR   PIRSF; PIRSF000193; Pyrrol-5-carb_rd; 1.
DR   SUPFAM; SSF48179; SSF48179; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   Amino-acid biosynthesis; NADP; Oxidoreductase; Proline biosynthesis.
FT   CHAIN           1..318
FT                   /note="Pyrroline-5-carboxylate reductase ucsG"
FT                   /id="PRO_0000450537"
SQ   SEQUENCE   318 AA;  33213 MW;  5A6E1827B39796A8 CRC64;
     MRNGAHRCES AMPGVTMTVL GCGKLGTAII QGLLRSCPKA SEAAPQKYLY PISTVIAAVR
     SKDRLESLIK SLVAEINDHT CPLDFVIANN VEAVRRADVV FLACHPNQAT ECLGGIGMQD
     AISGKLVISV LGGVSVATLE QAVYSSTRRP ASGQAPCHIV QAIANTAAAR QQSVTVVAEE
     ETANSHEKGS LCEDVLRRLG QVSYVSPDLM PAVTALCASG TAFFTTYLDA MIQGAVSEGL
     GEDVATRLAA LTMAGAANAV ISGEHPAAVT SRVTTPGGVT AEGLKVLREG DLRTLTAKAI
     SATTRRLRLV DEKSRKQS