FMQB_ASPFU
ID FMQB_ASPFU Reviewed; 418 AA.
AC Q4WLW7;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=FAD-dependent monooxygenase fmqB {ECO:0000303|PubMed:20804163};
DE EC=1.-.-.- {ECO:0000269|PubMed:20804163};
DE AltName: Full=Fumiquinazoline biosynthesis cluster protein B {ECO:0000303|PubMed:24612080};
GN Name=fmqB {ECO:0000303|PubMed:24612080}; ORFNames=AFUA_6G12060;
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.
RX PubMed=20225828; DOI=10.1021/bi100198y;
RA Ames B.D., Walsh C.T.;
RT "Anthranilate-activating modules from fungal nonribosomal peptide assembly
RT lines.";
RL Biochemistry 49:3351-3365(2010).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20804163; DOI=10.1021/bi1012029;
RA Ames B.D., Liu X., Walsh C.T.;
RT "Enzymatic processing of fumiquinazoline F: a tandem oxidative-acylation
RT strategy for the generation of multicyclic scaffolds in fungal indole
RT alkaloid biosynthesis.";
RL Biochemistry 49:8564-8576(2010).
RN [4]
RP FUNCTION.
RX PubMed=21899262; DOI=10.1021/bi201302w;
RA Ames B.D., Haynes S.W., Gao X., Evans B.S., Kelleher N.L., Tang Y.,
RA Walsh C.T.;
RT "Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation
RT of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the
RT flavoenzyme Af12070 from Aspergillus fumigatus.";
RL Biochemistry 50:8756-8769(2011).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, SUBCELLULAR LOCATION, AND
RP PATHWAY.
RX PubMed=24612080; DOI=10.1111/cmi.12284;
RA Lim F.Y., Ames B., Walsh C.T., Keller N.P.;
RT "Co-ordination between BrlA regulation and secretion of the oxidoreductase
RT FmqD directs selective accumulation of fumiquinazoline C to conidial
RT tissues in Aspergillus fumigatus.";
RL Cell. Microbiol. 16:1267-1283(2014).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=33705521; DOI=10.1093/genetics/iyab036;
RA Rocha M.C., Fabri J.H.T.M., da Silva L.P., Angolini C.F.F., Bertolini M.C.,
RA da Cunha A.F., Valiante V., Goldman G.H., Fill T.P., Malavazi I.;
RT "Transcriptional control of the production of Aspergillus fumigatus
RT conidia-borne secondary metabolite fumiquinazoline C important for
RT phagocytosis protection.";
RL Genetics 0:0-0(2021).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the antitumor fumiquinazolines that confer
CC a dual-usage capability to defend against phagocytes in the environment
CC and animal hosts (PubMed:20225828, PubMed:20804163, PubMed:21899262,
CC PubMed:24612080, PubMed:33705521). The simplest member is
CC fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from
CC anthranilic acid (Ant), tryptophan (Trp), and alanine (Ala)
CC (PubMed:20225828). The trimodular NRPS fmqA is responsible for FQF
CC formation (PubMed:20225828). Modules 1, 2 and 3 of fmqA are predicted
CC to activate and load Ant, Trp and Ala, respectively, providing for the
CC assembly of an Ant-Trp-Ala-S-enzyme intermediate that would undergo
CC double cyclization for chain release and generation of the tricyclic 6-
CC 6-6 product fumiquinazoline F (PubMed:20225828). The presence of an E
CC domain predicted for module 2 of fmqA is consistent with epimerization
CC of L-Trp to D-Trp during assembly to generate the R-stereocenter at C14
CC of FQF (PubMed:20225828). The FAD-dependent monooxygenase fmqB and the
CC monomodular NRPS fmqC then maturate FQF to FQA (PubMed:20804163). FmqB
CC oxidizes the 2',3'-double bond of the indole side chain of FQF, and
CC fmqC activates L-Ala as the adenylate, installs it as the pantetheinyl
CC thioester on its carrier protein domain, and acylates the oxidized
CC indole for subsequent intramolecular cyclization to create the 6-5-5-
CC imidazolindolone of FQA (PubMed:20804163). The FAD-linked
CC oxidoreductase fmqD introduces a third layer of scaffold complexity by
CC converting FQA to the spirohemiaminal FQC, presumably by catalyzing the
CC formation of a transient imine within the pyrazinone ring
CC (PubMed:21899262). FQC subsequently converts nonenzymatically to the
CC known cyclic aminal FQD (PubMed:21899262).
CC {ECO:0000269|PubMed:20225828, ECO:0000269|PubMed:20804163,
CC ECO:0000269|PubMed:21899262, ECO:0000269|PubMed:24612080,
CC ECO:0000269|PubMed:33705521}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:20804163,
CC ECO:0000269|PubMed:24612080}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24612080}.
CC -!- INDUCTION: Expression is positively regulated by brlA, a conidiation-
CC specific transcription factor involved in the early stage of asexual
CC development and necessary for conidiophore formation (PubMed:24612080).
CC Expression is also induced by the cell wall integrity (CWI) signaling
CC pathway that includes the mitogen-activated protein kinase mpkA and the
CC transcription factor rlmA (PubMed:33705521). Expression is negatively
CC regulated by the transcription factor sebA (PubMed:33705521).
CC {ECO:0000269|PubMed:24612080, ECO:0000269|PubMed:33705521}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of fumiquinazoline A and
CC C and shows a 19-fold accumulation in fumiquinazoline F production
CC (PubMed:24612080). {ECO:0000269|PubMed:24612080}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase 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; AAHF01000006; EAL89047.1; -; Genomic_DNA.
DR RefSeq; XP_751085.1; XM_745992.1.
DR AlphaFoldDB; Q4WLW7; -.
DR SMR; Q4WLW7; -.
DR STRING; 746128.CADAFUBP00007608; -.
DR EnsemblFungi; EAL89047; EAL89047; AFUA_6G12060.
DR GeneID; 3508390; -.
DR KEGG; afm:AFUA_6G12060; -.
DR eggNOG; KOG2614; Eukaryota.
DR HOGENOM; CLU_009665_19_1_1; -.
DR InParanoid; Q4WLW7; -.
DR OMA; KTRERWH; -.
DR OrthoDB; 462247at2759; -.
DR BioCyc; MetaCyc:MON-18828; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR GO; GO:1900781; P:fumiquinazoline C biosynthetic process; IDA:GO_Central.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 2.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; FAD; Flavoprotein; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..418
FT /note="FAD-dependent monooxygenase fmqB"
FT /id="PRO_0000444452"
FT BINDING 92
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 145
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 203..205
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 272
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 282..286
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 418 AA; 46550 MW; DE0EB6981F2104D7 CRC64;
MKLPAAAGDA IVIGPNAVRL IKSWGEQLCE EIEPHLSNAT HAEMLDHHDR FIVRHELAGR
GKGWFTNRGR LISILYEHAR KLGIDIRLGS RVTKYWEEDG RAGVIVNDRE RLAADCVICA
DGVHSAARAW LTGQVDTQQH SGWANFRAHM TTEQLAKDPE ASWVLQGTRE KDRVYVWFGD
GINLAIMTMK RGQELAWALM HTDKFNAHES WAGGRASIDD ALATLSPWPG RLRPSSVIRH
TLPEKLVDHA LIYRPPLDTW VSAGGRVMLI GDAAHPYFPV VGQGGSQAIE DGVVVATALE
LAGKENVPLA LRIRATLTEE NNVLMEAGNS RYPRATVIQL GSSTLQEHLF WPDWEAVAKD
PSVFAFPNPE WILGHDCREY THQVFDTVVR AVRGEGEYIP RNIPADGAYR VEDTYSPE
