Protein: Nonribosomal peptide synthetase 13 (EC 6.3.3.-) (Brevianamide F synthase) (Fumitremorgin biosynthesis protein A) (Q4WAW3)
Organism: Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293) (Neosartorya fumigata)
Function: Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of fumitremorgins, indole alkaloids that carry not only intriguing chemical structures, but also interesting biological and pharmacological activities. The biosynthesis of fumitremorgin-type alkaloids begins by condensation of the two amino acids L-tryptophan and L-proline to brevianamide F, catalyzed by the non-ribosomal peptide synthetase ftmA. Brevianamide F is then prenylated by the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl diphosphate, resulting in the formation of tryprostatin B. The three cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively. The putative methyltransferase ftmMT/ftmD is expected for the conversion of 6-hydroxytryprostatin B to tryprostatin A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate, resulting in the formation of fumitremorgin B. Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via the insertion of an endoperoxide bond between the two prenyl moieties. In some fungal species, verruculogen is further converted to fumitremorgin A, but the enzymes involved in this step have not been identified yet (Probable).
Interaction partners:
- Tryprostatin B synthase ftmPT1
- tryptophan synthase
- Tryptophan synthase
Sequence:
MAMALAVGAPSEQRGNLPYNTLKDGPTVDSMKATTDGKNGQGESAFWDTCVHTVFREHCQRAPNSPAVNAWDGSFTYAELDSLSDAIASVLILSGVGPESIIPIYMQKSRWTTVAILGVLKSGGAFTLLDPSHPRSRVEEISKEIQARFILTSEKLSKQCLEMFSVLVVEHLSRACLPSPGQAGHTRSRPENAAYIAFTSGSTGKPKGIVIEHRSYCSGARSHLKVFGIDSTSRVLQFASYAFDVSIMETLSTLMAGGCLCVMSESERSDPNLFVVSYKNLRISHCFMTPSFARTVPWTECCNPPPTLIVGGELMRPSDARAYKEMGIRCMNAYGPAECSVNVSVQSRVEAAVDPRNIGYTTGATAWIISPENPEELMPTGTVGELLVEGPIVGRGYLNDPKATRQAFIDTPAWLRRHRKGTSYQHRVYRTGDLASLDSITGALLLHGRKDAQVKIRGQRVELPDIEHHLQLTLPNDNAEVIVEKVTFSDDGSEKLIAFVLVRPSNTDSVIGNTGDRLFLAPQSQIMEQFAISKKHLQTHLPSYMVPDIFIPISTLPQTASGKTDRKALRTRAAALSRRDVQCFLLSPAGGKRPPSTPKEATIRSLYSNVLNLPIDLIGMDDTFLRLGGDSLQAIRLVAAARAAGLILQAKDILSSQSTLAEQSKRAGLIQTIDRTWESSPPFALLHGPTRHAIVDLAQKQCRVPSNLIEDIYPCTALQEGMFITSLKHPGMYTGQIIFDIPDRMELPRLRAAWLSVVSENAALRTRIIETHEGLMQAVIVDDFVWEEETDEMLLSSDGEALEITKIGVPLVRFRYRPRHRQLMMTIHHSIWDGWSLRLVHEQLHRAYIGRDLLPSTSYRSFIQYTQELQGADEFWASELAGVNAPIFPTLPSGNYRPRVNASHRHVVRNLASTGKEEHTAATYIHLAWSLLVAHYTDADETVYGVTVNGRSADVPGVENIVGPTIATVPTRIRVNEEDTVEMALDHVQDALARMIPYEQAGLQRISRCSRDASEACRFQTLLIIEAPTDSDVDCEKNEAGNFSIIGGTTQTGMDYTAFSSYAMMLVFRTSANKSAISFDITYDAQVIGHDEVERMAHQFEHVLRHIYTLATGRIGDISFIGPRDIEQVQQWNSSMPPADNRFLQELIFAQCSRRPQASAIISWDGSWTYRELWAHSSFFARQLQRYGVTRGTPVAVCLDRSRWSIAVILGVLLARGTCVLIDLLAPRQRVRDILQIAGTGILVHSHATATLTSGLCPTVVNVSFLAAQSDSSQPEFPFTLETWGGTPEDLAFIIFTSGSTGHPKGIEMPHRTLSTSISHHSAGMRVTSSSRVLHFSSYAFDVSIYEIFTTLAAGGTICVPSEFDRMNNLAGFIQDTQVNWAFLTPSTARSLNPADVPLLTTLVLGGEAVTHESVEVWAKGRSLINGYGPAEATICGVGNIPEAGWKSGVVGRIIGGLGWVTVPSDPNRLAAVGAVGELLLEGPFLARGYLNLPEVTKAAFIDPPSWRTRIPAPSPYSFLYRTGDLVRYQPDGSIQYVGRKDSRVKLRGQLVDLGAVEASVMRVYPAAGQVVADVLVSENTARLIAMVKLGPSVTENHDGPMFAAPDLVFNEAAASIQARLRAIVPAYMVPSMFIPLRHIPRTLTGKTDRRRLRDKILSLSHSDLQRYMMSSSTKTPMSDDNERRLQEIWAEVLQLPCEAIGREDSFLSLGGESLATMKMVALARRVGFMFAVTDVMNNTSLSTLARSRHLITEQAILTSSPSLSLPTIEGESLQEILRPLLNAGHIQGGNDIAAIHPVTAAQAFLVQRYPWSHFQFDLSGAVSPSKLQTACTALMARFTILRTVFVEHAGCLLQLVLREVPNRVHEITTNEPLDDFCNSVCQQQQDVCVVNSTTLPTLFTLVSNRQLNRHRLLLRLAHAQYDLTTIPLIVQSLADEYNRTLRSGFSADFGYYLSHHKRQNNDDRSHNFWKRYLSGSSMMSTNQTADPTTVQERVFHVTGSCIIIPTSHPPDITIATAVKAAVCLVLAARTGCTDIVIGQTVDARCSSADSTLDQIVGPCTNYIPYRLSVCCSKTALEYLRSAQAQHTTCLRYSSLDFDQIVAKCTSWPSSTQFGYIVQHQDTGAELALTLGGDTTSLPMTSYGRVFPQGEVWIGSTPCSTGLRIDVIALSAVLSQKDAQTMAEEVGAALEKLLGCGYRRLSHLIGNTFAT