ID   UCSB_ACRSP              Reviewed;         288 AA.
AC   A0A411KUP5;
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=Methyltransferase ucsB {ECO:0000303|PubMed:29373009};
DE            EC=2.1.1.- {ECO:0000305|PubMed:29373009};
DE   AltName: Full=UCS1025A pyrrolizidinone biosynthesis cluster protein B {ECO:0000303|PubMed:29373009};
GN   Name=ucsB {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: Methyltransferase; 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:0000305|PubMed:29373009}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. {ECO:0000305}.
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DR   EMBL; MH375765; QBC88146.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411KUP5; -.
DR   SMR; A0A411KUP5; -.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR013216; Methyltransf_11.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   Pfam; PF08241; Methyltransf_11; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   3: Inferred from homology;
KW   Methyltransferase; Transferase.
FT   CHAIN           1..288
FT                   /note="Methyltransferase ucsB"
FT                   /id="PRO_0000450531"
FT   BINDING         87
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:A6VDI6"
FT   BINDING         121..122
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:A6VDI6"
SQ   SEQUENCE   288 AA;  31826 MW;  3764BD6D30A075D7 CRC64;
     MIIQGNQLDS LPKAEDWEAF AESYKRIAEV AVMKPVQALL QCLDDRLPLS GAVGILDNGS
     GPGIIMSSLI ERYGPQLPPD CVLTCVDYAP AMIDQVDKAR IKAVEEDADS AWGRVEGKVL
     DALDLHSIAD ESQSHIAAGL LYNLTTDPAK CLSECKRTLQ PGGVLAVSAW EGNDWIEMLR
     VVPLIKPDLK TAIQPKWSTV DAVRWDLELA GFREVHVQRI PIKIPFTSHA LFVDTLMRYQ
     PRMVAMLRTF TEDEKTELRR LLMNEMKVIC PSQPGMMSGA VMVGAGVR