Protein
Malformin synthetase mlfA
Organism
Aspergillus brasiliensis (strain CBS 101740 / IMI 381727 / IBT 21946)
Function
Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of malformins, cyclic pentapeptides with a disulfide bond between 2 consecutive cysteins, that show potential anti-tumor as well as antimalarial and antitrypanosomal properties (PubMed:30560908). The nonribosomal peptide synthetase mlfA is responsible of the formation of the cyclic pentapeptide. MlfA probably acts iteratively on one amino acid and possesses multiple amino acid specificities since it is involved in the biosynthesis of multiple malformins, including malformin C and malformin A2. Malformin C corresponds to a cyclo[D-Cys-D-Cys-Val-D-Leu-Val] pentapeptide whereas malformin A2 corresponds to a cyclo[D-Cys-D-Cys-Val-D-Leu-Ile] pentapeptide (PubMed:30560908). The malformin biosynthesis clusters in malformin-producing fungi also contain enzymes involved in the formation of the disulfide bond between the two consecutive cysteins within malformins, in addition to additionnal tailoring enzymes such as methyltransferases or oxidoreductases. They are also composed of up to 4 major facilitator superfamily transporters, and transcription factors probably involved in the regulation of the expression of those clusters (Probable).
Similarity
Belongs to the NRP synthase family.
Sequence
MSRFSCIFPTLTDGYVPNPDHTRAAGRRTYTIDLSGWNGSSGQAESYILAAWGLVLSSYVGTDEVAFYVVPTTGPDTTALAELKVEGDMSRLSLTDAAEQLLHPKHVGAGQISGETANTIITFANDIESLFVTQTEESFLLLHVHRDEKGHISLTLTYYLSLLTDAQAANVCTAMSQALAVVTTDHPERLIKDLNLMSPTHIDHIWKFNANVPGPWEECFHDVVERHAANRPHSLAVDAWDMKLTYAELVREAHLLAAYLQQRGVRPGSVVPISFERSGAALVAMLAVSKAGGAFVSVPPNLPAGRLDAILEVIEAPFVVTWSKYEAFWSERLSTLPIDNYPKPSGDATVESLGKPDDLFYVIFTSGSTGRPKGCMLSHSNWLNGALRNAPSWKYGPESRVLQMLSHTFDMSLLEICTSLGSGACVCVPCTEEIETSVSDAINRWQVNHVIMTPSLARALKPDDVPGLKTMCLGGEAFPKEIVTMWSERINLWQFYGPSECSINSSSRPITRPDADPLNIGPPNSAACWVVDAQDYNKLVPVGAIGELLVSGPIVGMGYLKNPVKTAEAFLDQVGFVSKDDPQFGGFRFYRTGDHVRWNSDGTITFCGRADTQVKLNGQRLELAEVEYQLGLEDGVQYAIAMSPQTGRCKNNLIAILTVKGTNCSNQRNAADEIPLLDRRDPIIQQTVKKLRSQLQHALPRYMVPTIWAFVGRMPMSASGKIDRVQLRNWVQEMSQETFDAITGRSFEAEDHVLGLSRLEQEIQLAWAEALGLSAAEVGLQQPFVALGGDSIKALDAVARCRTRQIKISMVHILSCEGVREAASLAEVQETPAQQVAEMAVDYSDLWTRLSTEYDLGKLGVTQVEDVEDVFPCTTMQEGMFLGQIRRPGAYHMRFFHRVQLKGGCLPTVDRIQQAWASLIERHPSLRTIFVDDLSPDAIYHSVVLRSVPLELTMREVPRDLSPEDALAMFTDELVPFRPNAPLHRMLLLTCRGRVPYFMLEISHVIMDGYALSVFRREFIQACSSTGPLPRGPDYRMFANYHRTRQTDDSAKYWTNYLSDCVPCHIPTHAVIAPTDAPPEWPRNLQRRDFSFNNSAAFLQRCKERQVTLACAIRAAWALVLRAYTQSQDVCFGYVSSGRNVPVPEVETIFGLCLSMQVCRARLSESSTIASLARKIQEDYVASLPFQHYPLAEAQRGLKQTHGQGLFNTAISMEWVPPTAEDGDALLDLEEIREQDDPTEYDVAISVDIHEGHIKLGFLYWPNLTEFEIAHLAEALQGAMNCFAYQPDDALDSLTLLQASDVCSTLADGPTLLPLEAVRVNMLSMIDRRVTRQPDTPAIEGWDGSLSYKQLHEQSCWVARNLLHQGLQLGDRVLVCADRSSRTVATILGLVRAGCVLVLSNPTDPDKRLHWLAEKCNAALIIADPAYEKRFATAGSRVLLTTAVCSPAAWDYEFPALDEHDLISILFTSGSTGTPKGILMDHGALATSVLLGHGRTLRFSRQTRMLHFASLTFDAALAEIFTTLAHGGCICVPTEEDRLSDVPGCISRFAVNTAMLTPSVGRLLDPTALPMLKSLIMVGEPMSRLDVERFAPVLDLYNGAGPTETSIMVTIAGPMTPTDEPTNLGHSVAGVRLWVTEAEDPNRLAPLGAVGELIVEGRLVTRGYLDDGERTQQAFLPSLPWLPSQHALYRTGDLVRYADDGSLRYMGRKDTQVKLRGQRIELQEVEYHLRKSLQQAQVVVEMVIPEGKTRAQASLVAFVSGLTAADVESSSACNSEESMTISQVVLPKSTIQTLEEALPRHMIPSVYYALETIPLSVNGKADRRRLREMGASLLASSAANKSTADGKKEPAKWTAASELERTLLELWATTLGLEVEAIHGDDSFFELGGDSVSAMKLVATARDKFKLSLSVPQMFRYPTIRQLAAELGESPRSSTSSASSSTEDEFTISTPDDSSTNDGVDDDFLQLATAQLAQLAQEKGKKVDIAALLKQLQGGSSSSKTPSVSSSSSSSSSRKKKSSKAAFPVEAPGPVPEPFSLLNGDADVVEQVRAHAAEQCKIPHEDIEDIYPATALQEGMMALMARTPGVYTTALTCELSSQIDLARLHSAWDKAAEAHPILRTRIIMTDDNTAVQVVQRAKGLPWDRYTLQDGESIPNLTSDMTLGSPLLRLAEIHRHSKPPMLLVAIHHALYDGWSMPLLKQAVEDAYHGQTLQPQPFTPFINYLKEGKRAAQDFWTAHLDGFAGGVFPNLPSIDHHIQPSERRSRSLTIPTAVSRNQYTMATKIQAAWAVTVSRYAEDEDIVFGTVSTGRSAPVPAIDRMVGPTITTVPVRISLGDQAQRVSPLLQRVQEDGWNRMDHEHLGLQYIGRLSESAAAACRLQTLLVIQPREESHANSGATLLSGLQDSAELEGVDTYPLMLVCEPDGASLHLTAVFDPLVLDRTILERMLAHWELVLTQLWTEPDMAVVDLDAVSYSDKQTLVQWNVGEKIADGCAHDAVHEWSIRTPHAPAVCAWDGEWTYEELDKCSSLLASQILEHGVTSGDFVALYHEKSRWVAAGILAVFKAGGILVTLDPAHPKDRIRDILDQTQPRLILTSQSLLGEARELDTPVLCLQFAASQPVPERCSSPPTVSPTQAAYAPFTSGSTGRPKGVPLEHRGLAASTASVSRACLLRPASRVLHFASFAFDASIMEPLVAWHAGGCLCIPDETARQTDLARCIRDFDVTWAFLTPSCLRLITPDDVQCLEALALGGESMTPEDISIWCPRLNQMVQLYGPAECCFVAALTEVTKPSENRLIGRPNACRCWVVNPKSPERLAPLGAIGELMVEGITVGQGYINNPERTTQSFIQPPTWLQALYPDEEQPRHLYRTGDLVRYAGEDGKLTFIGRRDGQVKLHGQRIELADVEAHLRPLIPAKHNIVVEMISSVDNQHPLLAAFVEEPSPSQGPQEQHIGLIHPSEAQYALNVKTIDGALSRTVPQHMIPSMYLHISRLPLSSSGKLNRRQLREMVAQLPRQKLNEYAAGSCEMASQRPTTAKECEMQAIWARVLAADPDTIGLNDDFFRIGGDSISGMQIATKCNAAGMHITSADLFRHRTIAQLLFHLRNAKKRGDAISLPAEPVEEWVDLAPIQQLFFEIAPEGSSHFNQSLLLRTSRHISVEELTAGLDILVKRHSMLRASFRRSESGHWSQQVRSLDSPAGTFYRLATHNGITRESLPSVFTTSQTSLSIQEGPLLAIDLVELTDGSQLLYLVAHHLVIDLVSWRILHGELEQYLQTGSLEPVTESVPFLTWSRAQAEYSAKHLTPVSALPRFQEAHDEFDGARYWGIPPESNTFGQTSTFRFTLDQTATDTLFGTGNNVLGTRPVEILQAALWYSFTQSLTDRPYPSIYVEGHGREPWADSIDISGTVGWFTTMSPLVFAPWDSLSRTSMEDFLDALSYIKDQRRRVPANGWAYFTSRYLNDEGKVAYGRMKPVVEILFNYMGQYQEMTREDAILQLAGDDIQSGTGAADIADDVPRFSLIDVGAFTANGCLSFEFIFPECIQRDARLKLWVENCERMLLSAAKLLSNEGPRKTLSDFPLMPELTYEQLSQCFEHTLPSMGLSASDVVNIYPCSSVQQGMLLAQLRDPQAYQQRFKFHVKSDERRLTLEQVKDAWREVINRHDILRTLLLPVSDHGHLDQVVMAPGSLQHLVRIDATDVNLTQGIPHSINITRDSSGTVVCEWNVSHVLVDAMSVAVIQLEVSQSLDGLLGQHEKPGQYADYIQWVSRRDKTETQAYWQRYLEGVEPCLFPKLTSTSDNVKPEGTISAVRATWDRDARMDELCQKHGITLTNLFHIVWALVLGAYVGTDDVCFGYTTLGRDVPVDGVEMMVGPLVNVLATTVQLRDEDSILDALRTHQAHLTNSLQHQHHALADVYASIGLVGSQLFNTIVSLQDVSHFDAPDEQSTRLEVQPANDASEVCHYLLVYKCFIFFDVNFRKYDVALNIGVGSSSIQLVCSYRTLSLSAEHADTLLRTASHVLSEILRDPTQRIQEIEIISPECKEQLVKWNPTVPAPSDEYIHEKIQGQCRLHSSRQAVCAWDGIFTYAELDDLSSRLAVRLTRMGATSEHIIPIYSPRSRWTVIAILGVLKTGAAFTLLEVSHPMNRLQEVCKQIDASVIIAPASHATSAASLAPILVVLDNITSMTPGQSESSPAVRMPPASEALAYLIFTSGSTGNPKGVMVTHQNLCSNASIMTTSVNMTADSRVLQFASYAFDASLWEMLGALFAGACLVIPSESESKEDLAGCIDRMAVTWAFLTPSVARILKPERVPQLRVLALGGEPIAVSDLDTWRTHAQVVCAYGPSETAILASTTSPSTIPTVGKDIGMPTTCSLWIVDKRDYQKLAPLGATGELLIEGPNVSKGYLGDPEKTNEAFPVAPRWLSQLRQSPTRVYRTGDLVRFDQSTGTLRFVGRKDNQIKFHGQRIELGDIENHAQQALPNASTVIVDLISPGESQQSYLVAFVYQPDTSTQTADAIDPILLPPSESFRTDALAAQKHMHDRLPHYMVPTAFLPLNCLPLSNTGKADRKRLRHCALALSGSELNAYRATATAKRMPSTEAECIMQQLIATVLGRDASEIGMDDSFFHLGGDSVQAMRLVSEGRQQGLTLSLRTIFDSPRLDDLARHNSLVQDDQPAAASPATMHDTFSLIDKLVSTYPIDKAAVVDILPTTSFQRHWLDAQLKSYIVVDIPGRISRDRLFTAMQRVVDAHPILRTSFVPHDNTAVQVILRTAFAITDADLSTTTVEDLCRQDANAAIAPGAPYLRVILATGEFGYKLIMRLSHAQYDAVSLSLLMNDLGHAYENDTHELPSSYSPSFTDYITYQQRQKVDSTATTFWRHLLQDVPLTSLDLQPSKPSTSNGTPITRTRDINIATFPQLPNGITLATAVKAAWSIVLAQKTNSPAVIFGQVVHGRGIPLPGVEGIVGPCANITPVVARLSPQTTGLELLQALQDQHRSGLSYEAVDLDDALAYTKGWQAGSPRVQTIVQHQNNVMTDGMGLSLGEVKCGVDVRAVDHVPREVWVYSSVDENKPGMLEVKIMSSTLVLSEEVAEELMDLVVEKVVALLRDPRGVCV