The following text describes a protein:
Function:
Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of the mycotoxins phomacins, leucine-derived cytochalasans with potent actin polymerization-inhibitory activities and monocot-specific antigerminative activities. The first step in the pathway is catalyzed by the hybrid PKS-NRPS phmA, assisted by the enoyl reductase phmE, that are responsible for fusion of the leucine precursor and the polyketide backbone to produce a 2-pyrrolidone intermediate. The polyketide synthase module (PKS) of phmA is responsible for the synthesis of the polyketide backbone and the downstream nonribosomal peptide synthetase (NRPS) amidates the carboxyl end of the polyketide with the leucine precursor. Because phmA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase phmE. Reduction by the hydrolyase phmG, followed by dehydration and intra-molecular Diels-Alder cyclization by the Diels-Alderase phmD then yield the required isoindolone-fused macrocycle (Probable). A number of oxidative steps catalyzed by the tailoring cytochrome P450 monooxygenase phmB, the FAD-linked oxidoreductase phmC and the short-chain dehydrogenase/reductase phmF, are further required to afford the final products, phomacin D and phomacin E.
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. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. 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. Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase. CcsA also contains a polyketide synthase module (PKS) consisting of several catalytic domains including a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a dehydratase domain (DH), a methyltransferase domain (MT), and a ketoreductase domain (KR). Instead of a thioesterase domain (TE), phmA finishes with a reductase-like domain (R) for peptide release. PhmA has the following architecture: KS-AT-DH-MT-KR-PCP-C-A-T-R.
Sequence:
MGSSSKDYTNEPIAIVGSACRFPGGASEPSKLWDLLEHPTDVLKEIPESRFSVDGFYHPNGLHHGTTNVRHSYILDDDIRLFDAQFFGIKPIEANSIDPQQRLLMETVYEGLEAAGQSIQRLQGSQTAVYVGLMSSDYKDLLGNDQESYPTLVALHQAVQLLRSGDGTNVALAAGTNLLLNPDQYIAESKLKMLSPDGRSRMWDEKANGYARGDGIAVVVLKRLSQALEDGDHIECLIRETQINQDGKTKGITMPSATAQTALIRATYAKAGLDLSKPSDRPQYFEAHGTGTPAGDPIEAEAIHTAFFGGDLGEAGHDKLFVGSIKTVIGHTEGTAGLAAVLKASLALQNRAVPPNRLFDRLNSKIRPFYGDLEILTKAQEWPVLVPGSVARASVNSFGFGGANAHAILEAYEPPSLVSDDVLVTPLAPVQFSAASETALRGTLRKYAEFLEKNQDVNLRDLAWTLNTRRSVLAARTAVFGANALDLAHELQKRAEADVATLIPVASRSLPAKPRILGVFTGQGAQWARMGAELLDASPAVDRIISELEKSLSTLPDGPEWSVKGEILATGGASRVAEAAISQPLCTAVQIVLVDLLKSAGINFEAVVGHSSGEMGAAYAAGYLSAQDAIRVAYYRGRHLHLAGGLGGEQGGMMAVGTSFEDAEELCSLPEFQGRIGVAAINSGASVTLSGDLDTIEAAKEILDDEKKFARLLKVDKAYHSHHMIACSDAYRKSLADCSIKVLRPSRGSATWLSSVYGEDIVDYRKELTSEYWINNMVRPVLFSQAVEFAAAEKGPFDCAIEVGPHPALKGPALQVLQEFLGNSIPYTGLLSRDRDDKKAFAEGLGYLWQAFGENAIDHKSFDTFVAGASAPLPQITSNLPTYAWDHDRRFWHESRQYAANRTKPDPTHELLGTKCPDGTEQQCRWRNMLRPQEIPWLAGHQIQGQMVFPAAGYVSAAVEAVKFSNEGLPITTIEIEDFVIGQAIIFNDDYASVETQFTLTNIVSDHMSWSASFAFYSASQKHSLGMDLNASGRISALFGPPKDDVLPPSTGRELNMIDVDPEQFYNSLSKLGFGYTGAFKALRNLYRKMDVAMGEIQNPRSTDPAYNLLLHPATFDNAIQSIILAYCYPGDGRLWSVHLPTSIKKIRINPSLCENSAGQEAVLHFKSTITSGRSTEIQGDVELYDTNGVNSIMQLEGLHTKPLGHATPENDRTLFLETIWDTAEPTKELALLAQPDISKKAQLGLDIERVAFYYIRNLGHVTTKADREQAEDYHKHFFNYIDHTVVSVNNGTSLFAKKEWMHDTHEQVLDIIKSYPESIDMKLMYAVGEHLLPVIRHETTMLEYMREDDMLNDFYVKALGFDEYTETMADQVCQLAHRYPHMNVLEIGAGTGGATKRIFKKLGKRFSSYTYTDISTGFFEKAREVFSEVESKMTFKALNIEKDPIAQGYTEGSYDLIVASLVLHATHVMEDTMRNVRRLLKPGGYLIMLELGDYVDMRTGLMFGPLPGWWMGYDDGRKLSPTMSEDDWDKCMKKVGFSGVDAIVPRQEHVPISLAIMTAQAVDEHVEFIRNPFASDGMFLLGHHLTLIGGSTDKTAKLLEAALPYLRSFYKHVTTVKSLASLSTIELPFMGSVICLEDLDVAVFENLSTETLQGVQHLFTKSKSCLWVTQGRKDDNPYQNMTVGLGRVATLEMTHLRLQSLDFDVIDSSTAVIMAKSLLRFEATEAWEQQGLAKNLLWSVEPEMSYEKGSFRVPRLIPNHARNNRYNSSRRLITQNKDPRTSTIGLRWTSKGYEIHNESPASSGLAFDGRVELQVSHSSLEAIRITKADYAYLVLGTNLRTKEQAFAITPDRHSIVRVFDSWTVPYTMTTEEALRLLPLVQDHLMALATMSDFSSGEALILIEPRWRFARLLSNLAQEKGVKLILLTTRLDIKDQDWITLHPNAPRRIIQSHMPKTASRLISCTDDLEFEANVKACLPPNCKMQRTEIFSSRVSKLDSFSSMAFIPSSLRSAFVRAHHESSPGDKESIASVSDIVSRGKPAKATFFSWDSSPTIPVQITPVDLEPLFSSDKTYWLVGLTGGLGLSLCEWMIQRGAKYVVLTSRNPQVDAKWEAHMKAHDAVVRIYANDVTDRDSVRSVYKQIRDELPPIGGVAQGAMVLSDAMFVDMGLERVCKVVEPKVKGAIHLEELFSEADLEFFVFFSSMAYVTGNQGQSIYAAANAYMAALAAQRKKRGLAGSVINIGAIVGNGYVTRQLTDEQRDYLAHMGNVFMSEQDFHQIFAEGVVAGRPGNDDIPEIMTGLGLAHMDDSDKVTWFNNPKFSHCVLWPDDQGAAVGMSKQNVTVKSRLLLATTADEVNEAIQESFTMKLRSSLQIEDSVAILKMNAEELGLDSLVAVDLRSWFVKELNVEMPVLKILGGFTVAELVSAAQEQLPASLTPNFGKEIDPALKAAAMLEKAAKTETVPRITNEANTAAYREEVDEEEQEEDEADNRPNFFSSASKDATQSSERFAIDASHISKSREVAFKATLLAPPATRSKTSSSSSSFTSDPENDFMMKSQMSAATPLSSYNDEYITAEDIKFERVSPMSFGQARFWFLKFYLQDQTTFNITTSIRLSGRLNVETFANAVQAVGRRHEGLRTAFFTDRHNQPMQGILHQSVLHLEHLRVSSQEAIDIEYAKTKNHVYNIGGGETMKIILLSLADDLYQIIIGYHHINMDGMSLEVILSDLQKVYNQQQLARVVPQYLDFSESQRREHSTGKWGKEISFWKGEFADIPAPLPILPMSKKSNRSPLTKYASNTVKFKIDAATSAQIQIACKRAKASPFNFYLAAFKTLLYRTAGEEQNDICIGIADGGRNSEHVEESVGFFLNILPLRFKQDSAQTFLEALRDARSKVVAALANSRVPFDVILNEVNAPRAATHNPLFQAFINYRQGVQERRQFCGCDSEATQFDGSQTAYDISIDILANPGADSTVYISGQSDLYSEENVKLLAHSYLALIKSFAKNPASRLGRPPLYDPQDTHRALDVGVGPELTDTWPNTLVDRVDEMASRFGSQIALKGPRNQLTYSQMTDRIHSIASSLKSNKIGNCSRVGVLQDPSTDFFCSLLAILRIGAIFVPLELRLTSPRLAVIVEDSNIDAIIYDKANQKDLLTLGSGFQKVNVSLIPAKSTSTVVNEAQPGSPAVILYTSGSTGKPKGILLSHASWRNQIQSSTQAFRIPQGTGVHLQQSSWSFDIAISQTFVALANGASLLIVSKELRGDSIAMARMIVSDRITHVQATPSEMVSWLHDADANALRSSSWKFAMSGGEKMNSALIGEFKALGKSDLALVNAYGPAETTLAVGSAEIDILDPGALDTAFRLFPNYSVYILDSKKQPVPLGISGEVYIGGAGVATGYLNNDNLTKERFLPDDFAPERYLQNDWTIMHRSGDRGRLTADGLVLEGRVDGDTQIKLRGIRIDLQDIESTIVQHSKGAVRDAVVSLRKSGETQILAAHIVLSAAFSGNAKTILDSIQTSLPLPQYMRPATTLVVKTLPTNYSGKLDRKAVSELPLRPVSKTSVPVTKENKSPESELRTIWKQVLGDDITSSHEIDYETDFFHVGGNSLALVRVQGMLKAAFNVEPPVAQLFDNSTLGAMLNLISPASQTMSTEHSSLLPNVVEYSPQAAASSGTIDWEKETALTDDLYDAEINPTPRDQGLAFKTVAITGASGFLGKEILKRMVDDVHIDKIHAIAIRRHISDLPAIFSNAKVQVHRGDLNAPRLGLSETRAKEIFDETDTVIHNGADVSFLKTYKTLSKTNVGSTRELVKLCLPSRIPIHFISSASVAHLSGRASFGEESVSEYEPPQDGSDGYTATKWASERFLELVSEKFSIPVWIHRPSSITGAEAPALDLMTNLLQFSKTMSKVPYSPTWSGTLDFVSVESVAHDIVEEVKNDSAHSSGMVRFMYESGDLEIAVQDMQGSLAKQTGEEFDKVDVETWTREAVSEGLDELVAAYLSTAANLPIMFPRLIRDNKRRRIEQKVQEQPSRGSSLREVVGRWLWSRQ