The following text describes a protein:
Function:
Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of pyripyropene A, a specific human acyl-coenzyme A:cholesterol acyltransferase 2 inhibitor. The first step of the pathway is the synthesis of nicotinyl-CoA from nicotinic acid by the nicotinic acid-CoA ligase pyr1. Nicotinyl-CoA is then a substrate of polyketide synthase pyr2 to produce 4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one (HPPO) which is further prenylated by the polyprenyl transferase pyr6 to yield farnesyl-HPPO. The next steps consist of an epoxidation of farnesyl-HPPO to epoxyfarnesyl-HPPO by FAD-dependent monooxygenase pyr5 and a cyclization of the terpenoid portion by the terpene cyclase pyr4 to yield deacetyl-pyripyropene E. The 2 cytochrome P450 monooxygenases pyr3 and pyr9, and the 2 acetyltransferases pyr7 and pyr8 are involved in the conversion of deacetyl-pyripyropene E into pyripyropene A through several cycles of oxidation and acetylation steps. Pyr7 acetylates deacetyl-pyripyropene E to pyripyropene E which is oxidized to 11-deacetyl-pyripyropene O by pyr3, which is in turn acetylated into pyripyropene O by pyr8. Pyripyropene O is then oxidized to deacetyl-pyripyropene A by pyr9. Deacetyl-pyripyropene A is finally acetylated to pyripyropene A by pyr8.
Domain:
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (By similarity).
Sequence:
MKENEPVAIIGTGCRFPGGASSPAKLWELLRNPREIARKIPANRFNIDAFYHPDGDHHGTTNVQESYFLDEDVRAFDAAFFNISPTEAAAMDPQQRLLLETVYESLDAAGLRMDALQGSMTGVFCGALRNDYSQIQTMDPQALPAYMVTGNSPSIMANRISYYFDWRGPSMTVDTGCSSSLLAVHLGVEALQNDDCSLAVAVGSNLILSPNAYIADSKTRMLSPTGRSRMWDSQADGYARGEGVASVVLKRLRDAIVDGDPIECVIRASGANSDGRTMGITMPNAQAQQALILQTYARAGLSPQERPTDRCQYFEAHGTGTQAGDPQEAAAIHASFFGPKSVADPLDRLFVGSIKTVVGHTEATAGLAGLIKASLSLQHGMIVPNLLMQQLNPKIEAFAAHLCVPTECVPWPAVPEGCPRRASVNSFGFGGANVHVVLESYTARQITPSHNLPSSLPFVFSAASERTLTSVLESYATFLREHAAVSLPSLAVSMWTRRSAHRHRLTLIARSVEELQDHIDKELSRRATGTPSSIVSRPSSRPRRVLGVFTGQGVQWPQMGLDLIEASPQIQQWMADLQEALDQLPLEYRPEFSLLRELSRPASSSRVHEGLLSLPLRTALQIVQVNILRAVGIEFSMVVGHSSGEIVAAYAAGVLTAADAIRIAYLRGRAIHESRDSAGRMMAVNLTWQQAQAVCAAEPFSGRISVAAANSPSSVTLSGDAEGLRDLEWLLKSLGFTPRMLQVDTAYHSPYMKPCADPYRRAMQACPVAVAPSAARWYSSVYPGEVMTGQDQAQRTGEYWVENMLRPVQFAQALEAAVRETGAPDVIVEVGPHPTLRGPVLQTLSKVHSAHSTIPYLALAERGKPGLDCWAMALGLAWAHLGPSVVRLDGYVSLLDPGQSHVPLTSLPPYPFDRSQTYWAQSRISLNYNHCITPPNALLGVLSPETGPGEFRWRNYLRPEELPWLADRRVGSRSVFPETGYISMALEAARMMVETQGLRLLSVKDFTVHTPLPIQNDAIGTEILVTVNDIFSHDGVISALFRCEAAVSDEFVKCATAKMIMHPGDPDRALLPTQGQRALAVGPVDINGFYNSLRCVDYHCTGPFAGLTGLHRGCDLATGTVHVPSRDPDGPIILHPATLELAIQAMIAALGAPDEGLLTGALLSKTVDNIWVNPALCVSEKEMTVVGYLTDVDGDHIRGDVDIFTRNGQKAVQMEGVCLVYQPSGIAPTDRQVLSQTEWGPLEPSLKTASRSLPANVLELYSLRDELALLYIKQASDGLTDSGRNELDCDGTRLLAQMNQCIANAREGRQLAGSPERLDKSIEAFAARVGPSIDDSGLRAIAAVGQQRPHVLRESGHQRVVTWPHFDEGNEYLKQDVQVSHLVDNLISVVSQTCFRFPQMDILQIGTLGGSVHSVLREMGRSFRSFTYAAPSQPTDGPGLERPGEVQHRTFDVDRNPLEQGYQDHAYDMVLFTTARFPLEVAVAHIRRLLKPRGFLVLMVRTNPNITHLNLLFGHPARCTETCSGEQVITKEHWIELLSTNGFRVESLDAPPEMAGHQGFSLLLCRASGEYKEPSPRGDLLLVGGGDKNADCVISELAELVQGRFDQVLRSPSLDLMEITVRSELTALILVDDQDLTEASLSALRRLITTSKRALWVTCAKSDQPNGGLTRGLLRSIMASEQLSCQLQLLHITDPVGVSVEILATALERLVQASAAQECPDSCGLDNIEPEVEYDGSMFLIPRQYHNNSTGLRHLGRRQTVTGYVDLSQGVVQVLPPTTDATCERFRLLSVAQPPLTSDDGSTIHLRVRYSSLAAVRVAGAMFLRLVIGREVSSNNRMIALSSHIASQVIVPESWACSLPDTVSEAQEQAFLHVTAAALLAGYLFDQLPPFGTFVVHGADRVFQSIVHQIPTWRNVKVIFSTSTNNLDKDGAMLYLHEHSTARQLSQVLPSDVSAVAVLDRRGQGIYDRMLSLLPDNATRIQIDDLYRASASTMTPNGRVSLLVVRAFITACLVAYTSCEAVSLTSMDLVPTATVAEYPPTHCHQGIIDWNPSIPVRAEIPTASSQVQLSPKKTYILVGIASELARMACLWLAAHGARWILLTSSKPEPDAWWVEELSSRGTRIAFSTMNLIDGVSVTSLHHSIAHPFPPAVGGVLIQPGPLPDCSLSQLTAEVLQSRLHPVLKELQLLDELHETQPLDFWVLIGSISGTLGHADQALTAAMSERMATLVRQRRSRGRPASLVHLGEISGIDIPADGARPWWGPTAVTQRDIDEVLSEAVLCGGPNSFARSAEFIVGLRHQSLQTGRMAGPVPKLWPFYSYTATASQGQKPPSLPERRQSAKDLVAAATSREEKAEAIAACLMEKIRARLKLNADAPLSSDTLISELGVDSLVAVELRRWFAKQLAVDMSIVLILSGASVGELANAAASKLCNGNSELCTSSNLV