Protein
Hybrid PKS-NRPS synthetase ATEG_00325
Organism
Aspergillus terreus (strain NIH 2624 / FGSC A1156)
Function
PKS-NRPS hybrid synthetase; part of the gene cluster that mediates the biosynthesis of isoflavipucine (PubMed:21236704). The PKS part of the PKS-NRPS ATEG_00325 probably assembles a triketide from an acetyl starter and two malonyl-CoA extender units (PubMed:21236704). The poly-beta-keto intermediate would then be fused to the leucine unit by the NRPS part (PubMed:21236704). The resulting amide would be liberated from the PKS-NRPS through reductive release of the linear PKS-NRPS product from the enzyme complex (PubMed:21236704). Further steps in isoflapucine synthesis include a cyclization step, an oxidation step, a hydrolysis step involving a trans-amidation, and an additional oxidation step, leading to flavipucine (PubMed:21236704). Formation of isoflavipucine from flavipucine requires an unusual rearrangement (PubMed:21236704). Alternative rearrangement reactions could build up rubrobramide, representing a branching of flavipucine biosynthesis (PubMed:21236704). The enzymes involved in the post-PKS-NRPS steps have not been identified yet, but the putative oxygenases ATEG_003329 and ATEG_00330 encoded by the cluster could play a role (PubMed:21236704).
Similarity
Belongs to the NRP synthase family.
Sequence
MSSNEPIAIIGSSCRFAGGASSPSKLWDLLLKPKDLSKPPPESRFNLEGFYHPNAEQHGNTNIHGSYFLEEDPRCFDTVFFNISPKEAEAIDPQQRILLEVVYEAMEAAGLTLQGLQGSDTSVYAGLMIRDYMDVQVRDPDFFSQYMVTGTSSALNANRISYFFDWHGPSLTVDTACSSSLVAVHQAVQGLRAGESRVACVTGSNLLLGPELFISASNMHMLSSRSKMWDVSAEGYARGDGFASFMLKTLSNAIADGDHIEAIIRETGVNSDGRTKGITLPSPQAQADLIRDTYRRAGLDLSNPNDRCQYFEAHGTGTQAGDPREASAIHDAFFGAEGDDNKTGPKLVVGSIKTIVGHTEGTAGMAGMLKALLAIRHRVIPPNLHFNNLNPSVAPFYDRLTVPTESIPWPVVAPGTPLRASVNSFGFGGTNAHAIVESYEPDNRSSITGQNDGIVLPLVLSAHSDKALASVVENYAAFLRQTQQTLCLRDLAWTLHSRRSNLPVKAAFSGLSASDIAQQMQDRLESVRNTPGTELGIRSPAIASKKPSLLGVFTGQGAQWPTMGKHLIENSRTFRETIERLEKSLSELDDGPDWSLKGEILAQKAQSRVAEAALSQPLCTAIAIALVDLLHASGVSFTAVVGHSSGEIGAAYAAGVVTAEEAMKIAYYRGKYAKLAKGEHGAKGGMLAVGMGFNEAKEFCDQPAFKSRLGVAASNSPTSVTLSGDLDVVREAKELLDARKTFARMLQVDTAYHSHHMLPCADPYVSSLNASRIQPNEPAKSSCSWISSVYGSEGDPTAEELSATYWRDNMAQAVLFSQALERAMIECGPFDAVLEVGPHPALKGPASQTLRELSDGPLPYFGVLDRKRNDVVAFGDALASLWLHFGPSAVDFEGYAAASGPEDLPPPKLVKDLPAYPWDHSQIYWRESRLSREFRTRASPPHELLGHPLPAGSSEDGLRWRNILRIEEVPWIGDHRFQGQALLPTSAFCSMAVDAALKLAAGSVDPVADGIELHDLVIHNAVSIPDGSQGVEIITSIQRLEVTNHPLDAEVTVLFGPPDGSKVLKKAASARVILLHANSVDEPATLQAREKNLSSIDVPQFYQSIALVEGCIQTAYAAFSAPGDASLRPVFLPQKIERMSLRLPSVSSSDSWLIIDSFVTGVEKATPNTSPAFHADIEVADSVSGKLLVEIEGVTISSFSPTSAADDRELFLQTVWKPVVSEGLSVGNEQRKVANQAALDMEHQSILYLENLLANNLYLSGHLSQEFEWLLQLNLPSHSKGRQHNDGAEDVSHLDDFETLRAVAKNLPELIRGRLPGADIERQLQAFVETNSVFTRIKVGLHTLIDQIAHRFAHLNVLEIAPAHLSPSFDAFNDLVESISSYTLVTNSPSKDVAKYGKKLKHIGVEALHSDPSAIASALSGQKHDVVIASYLLNGQTASFSEEALRQFRKVLKAGGYLVLVEPTQEYVWSRIFLGVLLGSASNSDHGRDIGHHVSSVSLDGLLRKVGFSGIDSLLPRDANGPGDAISLFVTQALDETIDLLRHPLQPSALGILDGRRVLVVGGKTLQTSRLWHNIASILRPWTKEVHCIESFEALEEKDSTGIAGAIVLTDLDEPASKLLTTKSYQAISGLFAQAPHVLWVTQGALEANPEQAASIGLGHFLAQEHSSVHSQFLNLDTVEESEYKILGSFMRLLIPGIHDPQESRLWTTETEISVKNGRVFIPRVFPARGLNDRLNSHWRPIIQSANTLNDTTSLSASGSLHAATFTAQHFSSSSSAERRPILRTTQSIPIAINVSNGIYLYLSAGQVDDVGDVLAFTDTMSSRAPALATWKVPPAESGPVELSNILELTANVLVAQHIFDSLPAGNSVLLEPSYTLATIINELTKGADKKVHFLTTAAREETGSVTWTTIPPLASKRHILSALPPCPKLFFDLSPKPNRLSSRIVSLLPVDCALVGPGELFQLSSEGAEEVSTPWLQHVLLTVASSAVKLSRKATYPSSSTLILSDLLEHGIRNANAVTVVDWTQQTSVPVTVEPLEPSQFLSPAGTYVLIDIEQPLIQSIADWLIANGVRSLVAINSDIGERNGRELLDELKVKRLKVDLANLHDVKDVFDGLTKVTGVIYGGASAAMANFGEDDAPLQTLQNVEQSAHNLTTILENQEVGFFIILSSLQKDRAPVNAYFTSLAAHWKQRRLPTAVLSLESQVHSDPEGPFTHLSESDVHYALTEAISSAQSQNDVSAIWTGVKRLPRDIPASSQWSWLSKPLFAHYTQREQEAEPGSSQGEAQSMVQRLAASKSHEEASLVIQEFFLTRLAVMLTLSQESLSSSNDLTSLGVDSLSASDIRAWFLKELDVDVSILKILGGSTIADLCNEVAAGLTLQIGSQEEAESQPAVNSPEPVTAAPVPEQPTVERHVESQEPVVEAAVVASSSDSSSEGTMTPPSSRGINTPHTEITNLQLESVKSKACTAVQRREKMSFSQNRLWFPSAYLEQETPFNCTTSYTLTGPLDTARLENAFQRLIQRHESFRTAFYTDEVSGAAMQRVLASSPFQLRTMLGNKDDMQRVFRQIANYHFDLSVADTLVATLISHGPKDHTIVFGYHHIIMDGVSWQITLNDLARFYESDNPELPQLSQYIEFSVKQRQLVSSGAHDAKLSYWRKEFPSAPPLLPLFPFAKVGARKALTRYDTLDYIYDVDVSLVSKIKKASLAAKTTTFHFYLAAFVVLLNRFLEIDDVCLGIIDANRSDKTFLNTVGFLLDMLPLRLKVNKKERFVHTLRNTRAKAYNALEHSGVPLETILKELQVPTSATNTPLFQVLMNYRMGALRAPQMGDAKMNFLDYEDAKAPFDLAISIDEKDDGTGMLTFSMQDYMYDWEGAELLVKTYVHLLDTLATDSSQRINEVSLFDESLVNQSMVAGTGPVTGLDWAGTETISQRVDAMTAQRPDGVAVKDLNGKARTYAETQARVYALASSLQQAGITSGARVAVYCEPTVDTVALVLAIYRVGAAYIPLDVRNSHERLADVVRECKPTLILYHGATKHTLVDVAGDGQDALDIDTVPQSAAPIPDVSKLSDPAVILYTSGSTGKPKGIMLTHANLSLQFASISSALDLTDRDVVLQQSALGFDASLSQMFMALTNGGTLIHGSNRGDPVDLAALIEREGVTLTLIMISEMSALLQYGSDILSRCQSWRIALCGGEAFTVNLLRKFRDLNLPNLELYNAYGPTEASIMSSLGKVAYRRTDWGDGSVVPVGPPLPNYGVYVLDENFQPCPLGWPGELCICGPGVAEGYVGLPELTSSKFQPDQLRKPQGPSYDGWVRVYRTGDKARLLQDGSFVFLGRMDGDSQVKLRGIRIELNDISNSIVKTSKEAIVDAATIVKGTTSQTLVSFVVFAPAKVVDLERSNSSASAYLRQVIQSLPLPVYMRPAIAVPLERLPFTERGKLDTKALAAIPIQEDEETVNEELSETEQKLKQVWQDILSEQGMSLEIRRQSDFFSVGGNSLMLMRVRAKMLEVFGVSVPLAELFQASTLETLASRLDGNKTAESDNIVWNEETALDVSLPPAIAHPRDHPEKDLSVILTGSTGFLGRAIVRQLIADPRISTIHCLAVRPGRTLPEELVGSSKVIVYTGDLAAKRLGLSAPQAQEIFSSAAAIIHNGAEVSHMKSYHSLRPTNVDSTRQLVELALRSSIDSAVRTPAFHYVSTAGVGHLLGIPAFPEQSVSSSPPPVDGSDGYVAAKWASERILEQASERLGLPVFIHRPSNITGPDVGDRDIIHNVWRWSEVLRAVPDLVAAGAKGAFDFVGVETCAKGITDTLFVQASAGHLAYIHQSGENVIPVEEFGECLQRNGGADVELVPFDQWVDKAVQAGLDDLVASFLRGTKGAFQMPFLPKGLRQ