AGIB_ASPFN
ID AGIB_ASPFN Reviewed; 290 AA.
AC B8NY85;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=O-methyltransferase agiB {ECO:0000303|PubMed:31117395};
DE EC=2.1.1.- {ECO:0000269|PubMed:31117395};
DE AltName: Full=Aspergillicin biosynthesis cluster protein B {ECO:0000303|PubMed:31117395};
GN Name=agiB {ECO:0000303|PubMed:31117395}; ORFNames=AFLA_010550;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=26273902; DOI=10.1021/acs.jnatprod.5b00286;
RA Kikuchi H., Hoshikawa T., Fujimura S., Sakata N., Kurata S., Katou Y.,
RA Oshima Y.;
RT "Isolation of a Cyclic Depsipetide, Aspergillicin F, and Synthesis of
RT Aspergillicins with Innate Immune-Modulating Activity.";
RL J. Nat. Prod. 78:1949-1956(2015).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=31117395; DOI=10.1021/acschembio.9b00161;
RA Greco C., Pfannenstiel B.T., Liu J.C., Keller N.P.;
RT "Depsipeptide Aspergillicins Revealed by Chromatin Reader Protein
RT Deletion.";
RL ACS Chem. Biol. 14:1121-1128(2019).
CC -!- FUNCTION: O-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of the aspergillicins A and F, 2 cryptic cyclic hexa-
CC depsipeptides (PubMed:31117395). The hexamodular NRPS agiA catalyzes
CC the condensation of the six amino acid residues including N-Me-L-O-Me-
CC tyrosine, L-proline 1, L-proline 2, D-isoleucine, O-acetyl-threonine,
CC and L-isoleucine (PubMed:31117395). The starting condensation domain
CC (C1) of agiA probably loads acetyl-CoA which is condensed on the N-
CC terminus of threonine by the first module to yield O-acetyl-threonine
CC (PubMed:26273902). The second module then loads L-isoleucine. The
CC epimerase (E) domain on module 2 is probably involved in the formation
CC of the D-isoleucine moiety (PubMed:26273902). Modules 3 and 4 further
CC load 2 successive L-prolines (PubMed:26273902). Module 5 is then
CC involved in the condensation of O-Me-L-tyrosine produced by the O-
CC methyltransferase agiB and the N-methyl transferase (NMeT) domain on
CC module 5 probably catalyzes the N-methylation to yield the N-Me-L-O-Me-
CC tyrosine moiety (PubMed:26273902). The A domain of module 5 loads
CC preferentially O-Me-L-tyrosine, but it can also accept L-phenylalanine,
CC which leads to the production of aspergillicin G (PubMed:26273902).
CC Module 6 then loads the last residue, L-isoleucine (PubMed:26273902).
CC The C-terminal thiolesterase (TE) domain probably cyclizes the peptide
CC using the hydroxy group from threonine to form the cyclic depsipeptide
CC (PubMed:26273902). {ECO:0000269|PubMed:26273902,
CC ECO:0000269|PubMed:31117395}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31117395}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of aspergillicins A and F
CC but accumulates aspergillicins C and G. {ECO:0000269|PubMed:31117395}.
CC -!- BIOTECHNOLOGY: Aspergillicins show innate immunity-modulating activity.
CC Innate immunity is a good pharmaceutical target for the development of
CC immune regulators to suppress unwanted immune responses, such as septic
CC shock, inflammatory diseases, and autoimmune diseases. The innate
CC immune system also provides targets for the development of agents that
CC stimulate protective immune responses toward some diseases, such as
CC infections with pathogenic organisms and cancer.
CC {ECO:0000269|PubMed:31117395}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EQ963486; EED45171.1; -; Genomic_DNA.
DR RefSeq; XP_002385300.1; XM_002385259.1.
DR AlphaFoldDB; B8NY85; -.
DR SMR; B8NY85; -.
DR EnsemblFungi; EED45171; EED45171; AFLA_010550.
DR VEuPathDB; FungiDB:AFLA_010550; -.
DR eggNOG; KOG3178; Eukaryota.
DR HOGENOM; CLU_005533_1_2_1; -.
DR OMA; PAINLAF; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..290
FT /note="O-methyltransferase agiB"
FT /id="PRO_0000448727"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 155
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ SEQUENCE 290 AA; 32497 MW; 6E76606CC1A6B722 CRC64;
MRMLVSKSIF AEPEPGYYAH TPVSLVICAP NMPDLLSHRL EDGFRAASRH AEALAKLQYR
DPNAKDVLGF QLAFSTTKSY WDYVEEDDPE CGQRFSKAMR AVTVNKLGDV PKLYPFNKLV
DDGGIIVDVG GGMGQVAQSI LSHWHGLGLK CIVQDKFASK SGSTHPDLEM QSYDFFSPQP
VKGSAAYLFR HIFHDWPDDA CITILKNTVE AMNPHQSRIL ICDQIMEETN PSTAAVLYDI
DMMCLYGGKE RTLSEWEELL KAADQRLEIK NVFRSPNQVS GILEVQLCCD
