FSQC_ASPFU
ID FSQC_ASPFU Reviewed; 366 AA.
AC Q4WD44;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=N-methyltransferase fsqC {ECO:0000303|PubMed:27065235};
DE EC=2.1.1.- {ECO:0000305|PubMed:27065235};
DE AltName: Full=Fumipyrrole biosynthesis protein B {ECO:0000303|PubMed:25582336};
DE AltName: Full=Fumisoquins biosynthesis protein C {ECO:0000303|PubMed:27065235};
DE Flags: Precursor;
GN Name=fsqC {ECO:0000303|PubMed:27065235};
GN Synonyms=fmpB {ECO:0000303|PubMed:25582336}; ORFNames=AFUA_6G03450;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION, AND INDUCTION.
RX PubMed=25582336; DOI=10.1111/mmi.12926;
RA Macheleidt J., Scherlach K., Neuwirth T., Schmidt-Heck W., Strassburger M.,
RA Spraker J., Baccile J.A., Schroeder F.C., Keller N.P., Hertweck C.,
RA Heinekamp T., Brakhage A.A.;
RT "Transcriptome analysis of cyclic AMP-dependent protein kinase A-regulated
RT genes reveals the production of the novel natural compound fumipyrrole by
RT Aspergillus fumigatus.";
RL Mol. Microbiol. 96:148-162(2015).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27065235; DOI=10.1038/nchembio.2061;
RA Baccile J.A., Spraker J.E., Le H.H., Brandenburger E., Gomez C., Bok J.W.,
RA Macheleidt J., Brakhage A.A., Hoffmeister D., Keller N.P., Schroeder F.C.;
RT "Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus
RT fumigatus.";
RL Nat. Chem. Biol. 12:419-424(2016).
RN [4]
RP FUNCTION.
RX PubMed=30194285; DOI=10.1074/jbc.ra118.004227;
RA Lahham M., Pavkov-Keller T., Fuchs M., Niederhauser J., Chalhoub G.,
RA Daniel B., Kroutil W., Gruber K., Macheroux P.;
RT "Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the
RT amine oxidase family.";
RL J. Biol. Chem. 293:17021-17032(2018).
CC -!- FUNCTION: N-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of the isoquinoline alkaloids fumisoquin A, fumisoquin
CC B and fumisoquin C; as well as small amounts of fumipyrrole as a shunt
CC metabolite (PubMed:25582336, PubMed:27065235). The products of the
CC cluster lead to a brown coloration and are important for growth and
CC conidiation (PubMed:25582336). The nonribosomal peptide synthetase-like
CC protein fsqF, which lacks a canonical condensation domain, is required
CC for addition of a serine-derived dehydroalanine moiety to activated
CC tyrosine but is not essential for the subsequent steps leading to
CC isoquinoline formation (PubMed:27065235). A different enzyme, most
CC likely the ATP-grasp enzyme fsqD, is responsible for activation of
CC tyrosine (Probable). Three additional enzymes encoded by the fsq
CC cluster, the N-methyltransferase fsqC, the phenol 2-monooxygenase fsqG
CC and the FAD-dependent oxidase fsqB, catalyze the formation of the
CC isoquinoline ring system in the fumisoquins (PubMed:27065235,
CC PubMed:30194285). FsqB converts the fspF thiolation domain-bound
CC (2S,4S,5S)-2-amino-6-(3,4-dihydroxyphenyl)-4-hydroxy-5-
CC (methylamino)hexanoyl into isoquinoline (PubMed:27065235,
CC PubMed:30194285). The cyclization most likely proceeds via a two-step
CC mechanism, beginning with FAD-dependent oxidation of the methyl group
CC to an iminium species followed by electrophilic attack on the
CC deprotonated phenol (Probable). {ECO:0000269|PubMed:25582336,
CC ECO:0000269|PubMed:27065235, ECO:0000269|PubMed:30194285,
CC ECO:0000305|PubMed:27065235}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:25582336}.
CC -!- INDUCTION: Expression is positively regulated by the fumisoquins
CC biosynthesis specific transcription factor fsqA (PubMed:25582336).
CC {ECO:0000269|PubMed:25582336, ECO:0000269|PubMed:27065235}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete abolishment of isoquinoline
CC alkaloid production and accumulation of a series of benzyl pyrroles,
CC including fumipyrrole. {ECO:0000269|PubMed:27065235}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; AAHF01000012; EAL85694.1; -; Genomic_DNA.
DR RefSeq; XP_747732.1; XM_742639.1.
DR AlphaFoldDB; Q4WD44; -.
DR SMR; Q4WD44; -.
DR STRING; 746128.CADAFUBP00009218; -.
DR EnsemblFungi; EAL85694; EAL85694; AFUA_6G03450.
DR GeneID; 3505179; -.
DR KEGG; afm:AFUA_6G03450; -.
DR VEuPathDB; FungiDB:Afu6g03450; -.
DR eggNOG; ENOG502SQAU; Eukaryota.
DR HOGENOM; CLU_049766_0_2_1; -.
DR InParanoid; Q4WD44; -.
DR OMA; KYLWDET; -.
DR OrthoDB; 762504at2759; -.
DR Proteomes; UP000002530; Chromosome 6.
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; IPR019257; MeTrfase_dom.
DR InterPro; IPR017804; MeTrfase_EgtD-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR017805; SAM_MeTrfase_EasF-type_put.
DR Pfam; PF10017; Methyltransf_33; 1.
DR PIRSF; PIRSF018005; UCP018005; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR03439; methyl_EasF; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Signal; Transferase.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..366
FT /note="N-methyltransferase fsqC"
FT /evidence="ECO:0000255"
FT /id="PRO_0000438870"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 366 AA; 40933 MW; 3B3A6F8007143AF5 CRC64;
MSSNVQDIRG WPPPFANAAY QPDASSRRAR YGGLQVHNLR QATTANSLVP SIIQGLRAED
RELPSLLLWD DQGLSLFNAI LDSPEYYLAN KEWALLHNEV HNIVASISSG DRLVELGAGN
MKKTALILHT LQSQRKYIHY IACDVDRVAL QRGLRNLQAI FPASTSSIKI QGLVATYEDC
AAWLQRNPGS GHTSLMWLGN SLANFPPPEA SEYIRSFLST GASLILALDG CQDHEQIARA
YEGPSNQKFV LNGLRHANDV LGTDAFDVRN WSFLGRWNPE LWMHESFYAA KRDLTLKIGR
ETFVFRKGET IRSIRSGKWP KPKVVDICRE AGGDVVDWWM NPDESYGKST TLMGYLARVL
IDSVSD
