Protein
Nonribosomal peptide synthetase imqB
Organism
Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / NRRL 3357 / JCM 12722 / SRRC 167)
Function
Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of imizoquins A to D, tripeptide-derived alkaloids that serve a protective role against oxidative stress that are essential for normal germination (PubMed:29182847). ImqB is a canonical three-module NRPS that assembles the tripeptide backbone of the imizoquins via condensation of Trp, Tyr, and Leu-derived precursors (PubMed:29182847). N-methylation by imqF and phenol oxidation by imqC, followed by cyclization via the FAD-dependent oxidase imqH carry out the three-step transformation of L-tyrosine into tetrahydroisoquinoline (PubMed:29182847). Importantly, this sequence requires the presence of a free amine in the tyrosine moiety, indicating that isoquinoline formation occurs prior to peptide bond formation (PubMed:29182847). The imidazolidin-4-one ring of imizoquins could form following additional oxidation of the methyl-derived bridgehead carbon by imqH (PubMed:29182847). Lastly, O-methylation by imqG and leucine hydroxylation by imqE complete biosynthesis of the imizoquins (PubMed:29182847).
Similarity
Belongs to the NRP synthase family.
Sequence
MLSPAVCYHTDEGKNGYTFPNLETPKNGVVQTPVQYLIQTAPLHDFCSHQMVDLRTLLQCAWSRVIAQLDSTTDLKADAIYGTKSKSLLEGFISEVKKSQQSTQLENERILTEKLLLPLNPRGTSSLSWLQNDLLCATGGEYGEQSTGGFELAQCGSWIAISASFNPLIVSSRWVNDYIEVFRSFLVALVVGDDELSAPENYLTPEDCARIRNWNSAVPPEINASILDVFSEQVKAHPGSTAVSGWDASLTYQELEDCADQLAYQLQSRGVGPGMLIPLCFEKSAWTVVAIIAVISTGAAFVLLDASQPEARLRSIVMQTRATLMITSSQKKDLGRRLVPEVVSVQPTKSTKNSERSRALRPVIKPDSLLYVVFTSGSTGQPKGAMISHSNFVSAVHYRRSELYNVTPRVLDFASYSFDISIESTLAPLLLGGCVCVPSDASREADPSDAIKAFNVNQVMLTPSVARLVEPENVPSLRLLHLGGEQISRFDIERWPSTVKLINGYGPAECTVVSTANTVSPSSPEAHTIGRGLGAVTWVVDPADTGRLVPVGAVGELVIEGPLVGSGYLHDEGRTLAAFIVDPPWLRAFGRRGRLYRTGDLVSYNSNGTLTFIGRKDTQVKVNGQRVELGEIEHNLQQEIYNQGNCVVDVVVDLISVNSNSGKQSILLAFLGLERAAQERFAASGTPSVQELTSAMWEILEPINLFKVLPRYMVPSIYIPLWRMPLLPSGKINRLKLRSMGESLSVDDLAAFRKPQVATVDTQGRITPQEKLLQSLWGQIFPHCAGSIQPDDNFFSLGGDSLTAMKLVGLIRKHGIENKHSETIRIADILQWPRLADMARCITRVDDKQGDVQDALFDLLPDHIAPSNARQIAAPQCDVQPEQIVDIYPCTPLQEGLMALSAERSGAYIAQNIFELSDRTNIDTLRMAWTHIVMSSVIFRTRIVQLDSQTLAQAVVTVPIEWECYDGKLNDFVAIDRHRPMGIGKALMRLTVVTERSEESLLKCFLVWTAHHAVFDDWILNLITSLVGKMYHGRPPSSFHLTPYKRFIRHLQELNRESFSNYWRQELEGTNAAIFPHLPSAVDKPVADATANFAFSLNDSKLNVHASLPTILRAAWSILVSRHTQTDDVIFGETLTGRNAPVAGVEEMDGPTLTTIPRRVKVQNEMRVAEFLEEIRRHEINSIPYEGFGLQNIQKLSDDARTACQFATLLVIQRDPEVSFDSPMINVTEKVLHEDCGEDGKPYASFFTTYPLMVTISIKDNQINIYASFDSRIIERSQMQVLMHQLEVITRQVIQEPHEVVGGINCLTRKELHQIWSWNRLPWVPVSGSVHDSIAEVSNTRPTAPAVCAWDGSLTYGELDNLSTRLGSYLFKVGVEAESLVPLCFEKSVWTIVSMLAVIKAGGAFVLLDPTQPKQRLGEIIVRAKANYVLTSPLQYGMVSDLASEFNLTIVLVSKSPLDALTDDATVTDRMPQHLDSDRPLFVTFTSGSTGKPKGVISTHGSYLSGVNYRRSILQLPNLDMRVFDFASYSFDVSTDVILSTLLTGGCVCVPSDFDRKNNIPGAINALRVNAADLTPSVSRLLSPESVPGLKVLKLGGEANTAADHALWLGKTTLVNIYGPSECLVVTAKTVLPGIDPCNIGRGLGANTWVADPTNHDRLAPIGSIGELLVEGPILGRGYLDDQKQTDAVFIHNPTWLVKGLPGFQPGREGRVYKTGDLVRYNPDGTLHYIGRKDRQLKVRGQRVEPAEIEGAIKRHMQSKLGMTIDVVADLVTSNRDQRKRLIAFLGLNQVLESRGYSEKDHLGDTVLRDIMWEVTAGLEVLLSQTLPPYMVPSVYVPLRHIPLLPSGKTDRRKLQSAAASLSPEDLSFFRERPKAQNRAIATPKEEKLQKIWADALGVKSIQAEDNFFTIGGDSIAAMRLVGLARDQGLLLSVADIFQRPRLYEMAEKAAETGTELLDIPAFSLLPGANPYVIDEREVAAAQCGCSIELIEDIYPCTPLQEGLMALSTKTPGAYISQNVFQMGNATNTDLMKEAWDYVVRSNPIMRTRVILSARQDLVQVTVQEGIHWASHDSLDCYLKYDRNTSMGLGMPLTRLAWVDDEMTKRSFLVWTAHHAIFDGWVLSLVMENVIRVYHGKSLHVGPPFKAFIKYLKELERAQMDTFWQDEFSGITATPFPALPSSTYQPKADVETKLEMSFTWSTTSNVTSSTFLRLAWAVLVARLTASSDVIFGETLNGRNAPIPGIERMIGPTLTTLPRRIVLEDGLPVADLLHRLKDHEIAMMPFEHVGLQHLQELSADCQAACKFQTLFVVQRGMDHDMSEMSLTISGDVSNFNSYALMLTCAPESDKILFHASHDSNVISPEKMQDVLNQLQNVVMQLSKKMDRPLREINCLSEIDTQQIWKWNHQLPESISIPVHEIIAQQAREHPATEAVCAWDGTFTYRELDTLAGQLAYHLKELGAVSTPGYHIPLCFEKSAWTVISILAVMKAGGSFVLLDVSQPQDRLQHIVSHIKANYILSSPRQSDLASSLAANVVVVSSDFVRSLRQLHTPGPLNPNSALYVVFTSGSTGKPKGVIITHLNFASGVHYRQNVMHMPGFRLLDFPSYSFDASVESNLVPLMIGGCVCIASDELCQNNLSAAISSTNANAVMLTPSSATLISPENAHSLKQLHLGGEKLTAANIETWADKLKLVVGYGPAECAVTTTGRIVKGMVPQKENIGPAFGAVTWLVDPASHDRLVPLGTIGELLIEGPIVGQGYVNDPERTAAAFIENPPWLLAGGGMFAGRQGRLYKTGDLARYDSDGTLIFIGRKDTQVKIRGQRVELQEIEHHVYQYLRDLTGLGLSIVADLISTCSDIANPTLVVFIELEAVMTQKGYLPDPGPAVLYNEMKSMVPGLDEALRNALPRYMIPSAYVPRWKLPMMPSGKLNRKQLRSDAESLTAEQWNHFRSLISAVSPAARGREVATNDEAAVQRLWADILRIAEKQIKADDSFFTLGGNSITAMKLVELARRRGILFNVADVFAHPVLSDLASRIGRVETTPLNQDDLAYAPLQRLMSSNPTLIQGQSSNIPLVMIHDGGGTTYAYHRMGPVNRPLYGIHFPGYASGTAWKGGIKSLGRHYADLIQKSLLSGPIILGGWSSGGLISLEVALCLKSGPFEVKGVIMVDSVFPAPSLVDETFLAPSSSETNDTAMAADGTLAKMNMFQFNSMLKEYSPPRFEDLFQDLDASKAGLCHEQRSNVNPITEDTHHAERFPVHLLRASSTKASIGELDENMKSFLDATLGWEHYRPRLVSEVDLIDAEHYSLFSANTVAETTRHIRDFCDRITKSRKV