ID FTMH_ASPFM Reviewed; 427 AA. AC B9WZX7; D3TIT5; DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot. DT 14-APR-2009, sequence version 1. DT 25-MAY-2022, entry version 45. DE RecName: Full=12-alpha,13-alpha-dihydroxyfumitremorgin C prenyltransferase {ECO:0000303|PubMed:18683158}; DE EC=2.5.1.110 {ECO:0000269|PubMed:18683158}; DE AltName: Full=Fumitremorgin biosynthesis protein H {ECO:0000303|PubMed:23649274}; GN Name=ftmPT2 {ECO:0000303|PubMed:18683158}; GN Synonyms=ftmH {ECO:0000303|PubMed:23649274}; OS Neosartorya fumigata (Aspergillus fumigatus). OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes; OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus; OC Aspergillus subgen. Fumigati. OX NCBI_TaxID=746128; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RC STRAIN=BM939; RX PubMed=19226505; DOI=10.1002/cbic.200800787; RA Kato N., Suzuki H., Takagi H., Asami Y., Kakeya H., Uramoto M., Usui T., RA Takahashi S., Sugimoto Y., Osada H.; RT "Identification of cytochrome P450s required for fumitremorgin biosynthesis RT in Aspergillus fumigatus."; RL ChemBioChem 10:920-928(2009). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RC STRAIN=NIH 5233 / ATCC 13073; RX PubMed=18683158; DOI=10.1002/cbic.200800240; RA Grundmann A., Kuznetsova T., Afiyatullov S.S., Li S.M.; RT "FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the RT last step in the biosynthesis of fumitremorgin B."; RL ChemBioChem 9:2059-2063(2008). RN [3] RP FUNCTION. RX PubMed=16000710; DOI=10.1099/mic.0.27962-0; RA Grundmann A., Li S.M.; RT "Overproduction, purification and characterization of FtmPT1, a RT brevianamide F prenyltransferase from Aspergillus fumigatus."; RL Microbiology 151:2199-2207(2005). RN [4] RP FUNCTION. RX PubMed=16755625; DOI=10.1002/cbic.200600003; RA Maiya S., Grundmann A., Li S.M., Turner G.; RT "The fumitremorgin gene cluster of Aspergillus fumigatus: identification of RT a gene encoding brevianamide F synthetase."; RL ChemBioChem 7:1062-1069(2006). RN [5] RP FUNCTION. RX PubMed=19763315; DOI=10.1039/b908392h; RA Steffan N., Grundmann A., Afiyatullov S., Ruan H., Li S.M.; RT "FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, RT catalyses the endoperoxide formation of verruculogen in Aspergillus RT fumigatus."; RL Org. Biomol. Chem. 7:4082-4087(2009). RN [6] RP FUNCTION. RX PubMed=21105662; DOI=10.1021/ja106817c; RA Jost M., Zocher G., Tarcz S., Matuschek M., Xie X., Li S.M., Stehle T.; RT "Structure-function analysis of an enzymatic prenyl transfer reaction RT identifies a reaction chamber with modifiable specificity."; RL J. Am. Chem. Soc. 132:17849-17858(2010). RN [7] RP FUNCTION. RX PubMed=23090579; DOI=10.1039/c2ob26149a; RA Wollinsky B., Ludwig L., Xie X., Li S.M.; RT "Breaking the regioselectivity of indole prenyltransferases: identification RT of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of RT the regular C2-prenyltransferase FtmPT1."; RL Org. Biomol. Chem. 10:9262-9270(2012). RN [8] RP FUNCTION, AND PATHWAY. RX PubMed=23649274; DOI=10.1271/bbb.130026; RA Kato N., Suzuki H., Okumura H., Takahashi S., Osada H.; RT "A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in RT Aspergillus fumigatus strain Af293."; RL Biosci. Biotechnol. Biochem. 77:1061-1067(2013). CC -!- FUNCTION: 12-alpha,13-alpha-dihydroxyfumitremorgin C prenyltransferase; CC part of the gene cluster that mediates the biosynthesis of CC fumitremorgins, indole alkaloids that carry not only intriguing CC chemical structures, but also interesting biological and CC pharmacological activities (PubMed:18683158, PubMed:23649274). The CC biosynthesis of fumitremorgin-type alkaloids begins by condensation of CC the two amino acids L-tryptophan and L-proline to brevianamide F, CC catalyzed by the non-ribosomal peptide synthetase ftmA CC (PubMed:16755625). Brevianamide F is then prenylated by the CC prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl CC diphosphate, resulting in the formation of tryprostatin B CC (PubMed:16000710, PubMed:21105662, PubMed:23090579). The three CC cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and CC ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to CC 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and CC fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively CC (PubMed:19226505). The putative methyltransferase ftmMT/ftmD is CC expected for the conversion of 6-hydroxytryprostatin B to tryprostatin CC A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13- CC dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate, CC resulting in the formation of fumitremorgin B (PubMed:18683158). CC Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via CC the insertion of an endoperoxide bond between the two prenyl moieties CC (PubMed:19763315). In some fungal species, verruculogen is further CC converted to fumitremorgin A, but the enzymes involved in this step CC have not been identified yet (Probable). {ECO:0000269|PubMed:16000710, CC ECO:0000269|PubMed:16755625, ECO:0000269|PubMed:18683158, CC ECO:0000269|PubMed:19226505, ECO:0000269|PubMed:19763315, CC ECO:0000269|PubMed:21105662, ECO:0000269|PubMed:23090579, CC ECO:0000269|PubMed:23649274, ECO:0000305, ECO:0000305|PubMed:16000710}. CC -!- CATALYTIC ACTIVITY: CC Reaction=12alpha,13alpha-dihydroxyfumitremorgin C + dimethylallyl CC diphosphate = diphosphate + fumitremorgin B; Xref=Rhea:RHEA:35971, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:64531, CC ChEBI:CHEBI:72764; EC=2.5.1.110; CC Evidence={ECO:0000269|PubMed:18683158}; CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:18683158, CC ECO:0000269|PubMed:23649274}. CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase 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; AB436628; BAH24002.1; -; Genomic_DNA. DR EMBL; EU622826; ACF22981.1; -; mRNA. DR AlphaFoldDB; B9WZX7; -. DR SMR; B9WZX7; -. DR BRENDA; 2.5.1.110; 508. DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central. DR CDD; cd13929; PT-DMATS_CymD; 1. DR InterPro; IPR033964; Aro_prenylTrfase. DR InterPro; IPR017795; Aro_prenylTrfase_DMATS. DR InterPro; IPR012148; DMATS-type_fun. DR PANTHER; PTHR40627; PTHR40627; 1. DR Pfam; PF11991; Trp_DMAT; 1. DR PIRSF; PIRSF000509; Trp_DMAT; 1. DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1. DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1. PE 1: Evidence at protein level; KW Alkaloid metabolism; Prenyltransferase; Transferase; Virulence. FT CHAIN 1..427 FT /note="12-alpha,13-alpha-dihydroxyfumitremorgin C FT prenyltransferase" FT /id="PRO_0000424114" FT BINDING 94 FT /note="Substrate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 105 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 192 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 194 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 268 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 353 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 355 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 419 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT BINDING 423 FT /note="Dimethylallyl diphosphate" FT /evidence="ECO:0000250|UniProtKB:Q4WAW7" FT CONFLICT 165 FT /note="R -> K (in Ref. 2; ACF22981)" FT /evidence="ECO:0000305" FT CONFLICT 171 FT /note="P -> A (in Ref. 2; ACF22981)" FT /evidence="ECO:0000305" SQ SEQUENCE 427 AA; 48584 MW; 26F23D63CE60F100 CRC64; MTIPTEISCP EEDAFQLLDK FSWFPSDDQR RWWEYTGPYL LKLLRDAKYP QKDQVPCLYL LQQLLVPYLG TFPVVGQAPL PWWSNVTTYG VPFELSWNLL HNIVRIGFEP LSHLAESGVD AFNKTAPEEC VSRLACLDNT IDLARFRHFQ HHLLVTPEEE TWLLREKAPL PKSGRGQQTL AVEFQNGGIS AKAYFFPGMK SLATGLSPGK LILDSIERLA LPGLKEPVHH LRSTLGLQDD GHPTDTAIAP FLLGVDLCTP ERSRLKFYVT DQVVSWDRVA DMWTLRGKRL EDPQCADGLA LLRKLWDLLA IPEGYRSNIR PDFAFGTPPP EDYRPVMMAN WTLSPKKKFP DPQIYLLTVG MNDAVVMDAL VAFYEVLGWT DLASTYKDKV ASYFPGPDFT KTNYIHSGVS FSYRHSKPYL SVYYSPF //