Q4WLW5 · FMQA_ASPFU

Function

function

Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of the antitumor fumiquinazolines that confer a dual-usage capability to defend against phagocytes in the environment and animal hosts (PubMed:20225828, PubMed:20804163, PubMed:21899262, PubMed:24612080, PubMed:33705521).
The simplest member is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic acid (Ant), tryptophan (Trp), and alanine (Ala) (PubMed:20225828).
The trimodular NRPS fmqA is responsible for FQF formation (PubMed:20225828).
Modules 1, 2 and 3 of fmqA are predicted to activate and load Ant, Trp and Ala, respectively, providing for the assembly of an Ant-Trp-Ala-S-enzyme intermediate that would undergo double cyclization for chain release and generation of the tricyclic 6-6-6 product fumiquinazoline F (PubMed:20225828).
The presence of an E domain predicted for module 2 of fmqA is consistent with epimerization of L-Trp to D-Trp during assembly to generate the R-stereocenter at C14 of FQF (PubMed:20225828).
The FAD-dependent monooxygenase fmqB and the monomodular NRPS fmqC then maturate FQF to FQA (PubMed:20804163).
FmqB oxidizes the 2',3'-double bond of the indole side chain of FQF, and fmqC activates L-Ala as the adenylate, installs it as the pantetheinyl thioester on its carrier protein domain, and acylates the oxidized indole for subsequent intramolecular cyclization to create the 6-5-5-imidazolindolone of FQA (PubMed:20804163).
The FAD-linked oxidoreductase fmqD introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzing the formation of a transient imine within the pyrazinone ring (PubMed:21899262).
FQC subsequently converts nonenzymatically to the known cyclic aminal FQD (PubMed:21899262).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
18 μManthranilate
230 μMATP
17 μMsalicylic acid
29 μM2-chlorobenzoic acid
32 μM4-chlorobenzoic acid
74 μMbenzoic acid
416 μM3-aminobenzoic acidATP
1900 μM4-aminobenzoic acid

Pathway

Alkaloid biosynthesis.

GO annotations

AspectTerm
Cellular Componentcytoplasmic vesicle
Molecular Functionligase activity
Molecular Functionphosphopantetheine binding
Biological Processfumiquinazoline C biosynthetic process
Biological Processnonribosomal peptide biosynthetic process
Biological Processsecondary metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Nonribosomal peptide synthetase fmqA
  • EC number
  • Alternative names
    • Fumiquinazoline biosynthesis cluster protein A

Gene names

    • Name
      fmqA
    • Synonyms
      NRPS12
      , pesM
    • ORF names
      AFUA_6G12080

Organism names

Accessions

  • Primary accession
    Q4WLW5

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasmic vesicle
Note: Does not localize to endocytic vesicles, vacuoles nor mitochondria (PubMed:24612080).

Keywords

Phenotypes & Variants

Disruption phenotype

Abolishes the production of all fumiquinazolines (PubMed:24612080).

Miscellaneous

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004165531-3955Nonribosomal peptide synthetase fmqA
Modified residue840O-(pantetheine 4'-phosphoryl)serine
Modified residue1917O-(pantetheine 4'-phosphoryl)serine
Modified residue3459O-(pantetheine 4'-phosphoryl)serine

Keywords

Expression

Induction

Expression is positively regulated by brlA, a conidiation-specific transcription factor involved in the early stage of asexual development and necessary for conidiophore formation (PubMed:24612080).
Expression is also induced by the cell wall integrity (CWI) signaling pathway that includes the mitogen-activated protein kinase mpkA and the transcription factor rlmA (PubMed:33705521).
Expression is negatively regulated by the transcription factor sebA (PubMed:33705521).

Interaction

Subunit

Interacts with the mitogen-activated protein kinase mpkA.

Protein-protein interaction databases

Structure

3D structure databases

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region293-691Adenylation 1
Domain806-879Carrier 1
Region916-1187Condensation 1
Region1371-1766Adenylation 2
Domain1880-1956Carrier 2
Region1970-2261Epimerase
Region2438-2724Condensation 2
Region2906-3299Adenylation 3
Domain3422-3498Carrier 3
Region3541-3805Condensation 3

Domain

NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (PubMed:17464044).
Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:17464044).
Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (PubMed:17464044).
Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase (PubMed:17464044).
NRPS12 has the following architecture: A-T-C-A-T-E-C-A-T-C (PubMed:17464044, PubMed:20225828).

Sequence similarities

Belongs to the NRP synthetase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    3,955
  • Mass (Da)
    437,813
  • Last updated
    2005-07-05 v1
  • Checksum
    C66E17E07E1F5296
MERLEAKNQTTKHGERMAPQRYSVLRDEKCLFPVRNDGKLLVDEWRVTELAISSGEKGLKLCRTTCPTAGADPRYLAAAAWALLLWRFAEVDTVQIGLQDIPPGANEDILEAGLKRGMKVLAASRRQVQLLNELWQGDTWSISDADPTCYSYFDTGIVICRGNSQDCLAKCRSPNQLRKANGEACNVLLVLELDLDSNWRKCFLAYKTTVLTDIQATHLKSSFEEVVELARAGRGIPLSEICLVSRRQLDQIGKWNERALVQPKFKAMHQVVHDRATDRRHHPAVIAADRALSYSELETLSLKVAYRLRGSGVQPGDLIPVCFCKSSWAIVAMLAINKLGAAFVPLDPSQPVNRLKSITRQLDATLAVTSPENQSLVEDLVTTTVVVSETTVSELVDVHNEIVLPACDPGAPAYCLFTSGSTGKPKGCVVDHAALASVATHSHALHLGPTSRVLQFASFTFGVSLIEVWCTLAAGGTVCLPSDSDRVSRLADAIRSMGVDWCILTPTVLATLEPEAVPNLRTILVAGEPLKKAQFSLWAERARLFQAYGFTEWAGICCVSPQIRSIGDVGIIGTPANARCWLVEPGNPNQLAPIGAVAELAVEGPSLAQGYLHDPEKTAATLIPPPRWRAQYGHADGKRIYTTGDLVYYDSNGMLRYVSRKDRQVKIRGQRIDLAEPEYHIAQACCTIRNVVLDAIVPADSNGDAILVAFVLPSRDESSSNGGHDSPLFAVPDDHFTSSVRQLTSFLEDKLPDYMVPRLFLQLKETPVTITGKIARQKLREAAEALRHDELVALAGLETRVLPPNTHKETLIHQLVVELLHLPPEMVGMNHNFFSLGGDSVSVMKLVSRAKRVGLSFTVKDVFRSPQLGDLARLTDVVNSGAAQHMPPFSLLDRGAQPGLLSMAAKICQVESSMIQDIYPCTPLQEGMMTLSAAKAGSYIARFVYRLEEHVDSPRFRRAWEMTVEATPILRTRIISASDGRLYQVVIQEKFRWDDDGQPSGECVQNGQDRHMLLGEPLTHAALVRDRNQDGSLSTVFVLTMHHSVCDRWSVGLIMDSVETAYTGQTLTTNSMGPFLQYIQQLQGGDAFWRSQFVGVKAEVFPSLPSPEYTPTPTETIDLSVELRDAVPGGHTIANAIRLAWALVISHYTSCSDVVFGVTISGRAVPVPDIERIIGPIIATVPLRVRLKESSTVLEALKAIQDQSMEMIPFEQLGLRQIRKLSPEAEEACNFQSQLVVQPAWGDENRSLFATCEAGAAAEGGFAAYALSMICQLVGSSQIDVRTEFDPKVIQAPIMQRIVHHFVYTLQYLLAHPDARVAEIPVVSPGEKQLLRQWNGIVPPASHQCVHEIIQQRQIERPTSTAVWAWDGQLTYAELGELSDRLAEYLATKGVQPEVIVPVCLEKSYWTTVAMLGISKAGGAFALLDPSQPEQRLQSICHQLNSAVILTSEKNRDLAGKLASHPIVLSLQSSRRWGHGPAKQAPATARPDHTLYVAFTSGSTGTPKGVVIEHRSFCTSALALNRITGVNSESRMLQFAGYSFDGSIMEMLSALMAGACVCVPSEFQRRNELVAAAAKFELTHAHLTPSVARHLLRGNPEFTKTLVSVGEPMTASDVADWASNGQCKVMNGYGPAECAVSTTIQAAVTSASDPKNIGFPVAGVCWVVHPENHDILLPPGAVGELLIEGPTLARGYLNEPDKTAAAFIPLPAWIKDIRPEQPHGRLYKSGDLVRYNADGSFQYIGRRDSQIKLRGQRIELDEVEKHVYQCWPGVIAVVAVEMVSFTPATQTLVAFVVVEEHVDTTGDILAAPTQEFTGQVAVAQARLREAIPAFMVPEIFIPLLVLPQSASGKTDRRRLRSIATACTREKLAAYGAVGTGTKREPTSVAEREMQAIWAQALNLPLAEIGMDDSFYQLGGDSITAMQVVAHARSKGLAVTMDSILRLKSISKIMSHESSLSPAIVHIDEEEDVWFALSPIQQMFFDRQPSGWDRFSQVFLLRVSQPVTASQLQMALHTLVSKHPMLRARFAKQHDGSWRQVITSKIQESYRCRSHRLNRRSSVDGVVSSGACSLSIQKGPLIAVDLMSREDGAQYLSIVIHHLVVDLVSWRIILADLEAMLRGENPMANHSTPFQTWCRLQAEYARQYLSPQHAFPTDLPDHYHQDPSVFWGLAGQPNLVRDSRRQVFTLDEHTTRQLLGAANAAFATRTDEVLHAVLLYSFLKVFPHRIAPLTFSEGHGREPWDSAIDLSQTVGWFTTMWPVVAELQQNHSFLEVVCRVKDARRAVPCNGWAYFVSRYLNPSGRQAFQQFHPVELVFNYAGEYQQFNQAGAFFIPDMPEYQGSLDAGEQIQRFGIFEVFASVVRGCLQFQFMYNRYMKHQLEIQKWIESCRQTLIEGCSTLIAAKPSRTLSDFPLLPLTYSTLRELLDVTLPTAGVSVENVEDIYPCSPSQRGMLIAQAKAAHNYNASVTWSIRSRIDSRPNVARLKAAWCEVVKRHAILRTVFVESPWPESYMDQVVLQNVSPEFVFCRGSDSLPQSISSPGQTRWSKGQCQHIMRVWERDNGDILCRLDLSHAIMDRTTLAIIQKDLSLAYDERLLPGRAPLYRDYISYIYQQDSESARQYWQGYLEGVEPCEFPTLNPVDPSITKEWGNLYRTLEDRRRLEEFCRTHSVTPWNVAGLAWAMVLRSFTRTDSVCFGYVKSGRDLPIDGIAGTAGPVFNPLPCRVHLTERLTVRETIGRLQEEYLQSLAHQSFPLSDIHRLAGVTSGVLFNTSVAVQTEVASEAEEAKRSLEFTTVAMEDGTEDDMVITLVPRGGELVLHLRHRSRTLTTDQASTVLATFEKALCSILANAEAPMTSIDVFSDHDKAILWSRNRRVPDAVESCVHELIQKHCVERPHSPAVNAWDGAFTYGQLDELSSRLAVYLAAQGVGPNVVVPLCFEKTRWTPIAMMGVMKAGGAFLLLDPSYPLQRLKDICADIDCRLVVSSTTHEAMSRELASTVVVVGEDRHHWQLENTSHTITMPKVRPADALYVVFTSGSTGKPKGVVIEHRSYCSGALDHIRSYNLTPQSRVLQFSSYAFDISIVEQLSVLIAGGCICVISESQRKNSLGEAATALQANHAMLIPSVARLVRHEDLSTITSLSLAGECMQETDVSYWAQHVRLMNGYGPAECSALSLVQPCVLPHSDPHDIGYPVGSVAWVVDPHDHHKLVPNGAVGELLIEGPIVGRGYINNAEKTAEVFIEPPTWLRTLRGHCTSRLYKTGDLVRANPSGSLSILGRKDRQVKLRGQRLELGEVEANVQHCFPGALDVVADLLPSSRGGKPQLVAMVFQNAERAARIAPESDSKLIAEPSVDFMQSATTAETRLRQTVPNFMVPSMFLPLAQIPRTHSDKVDRNSLLKAVAAMSSIELQAYKASVDAGHCSTRAPSTEEEKKLAEIWADVLKVPVEHIGADDNFLLSGGDSIDAMKAAAFCRAAGMALSVADIFAHPVLSDLAKVAVPKSLNGSSTSHQPFSLSPVDSPKDLHMSLMEQGLVPPGSALADLLPGTQAQQFFIERGTFHSYNFSIRGPLDRCRLQKTCTAILSRHSILRTKFLQYEGRLIQIVLDNLETPFTHYTTDGDLLEFCKSLWERDLAALDGLGRLPCKFTLVSRSEQEHVFTIQISHAQWDGVSIPRLFSDIAAIYNQIPLPSTTHFADYVYHRSSRDERPAFDFWKKYLRGSSMPVPFPATNCQDREHKTQWTFQGIKNPRLPAGITMASLVKAACGFHLCQLLSQNDVVFGHTVNGRNLALDNVEALLGCCLNFIPLRVMLQPSWTVLDLLAHVQEQYTRALPHEHLELRDIFRHSTPWPADTQLSFIVQHQNIELHHNIALDGLQVQYSKFAQFDPLTEVWIFSEPHPDRLEIQVCANTRVLSEDQARALCRRLCDLIEFFSASPDCPLSKVVDHMDRPGLLAEEKVLN

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AAHF01000006
EMBL· GenBank· DDBJ
EAL89049.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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