Protein: CLZ14_COCLU
Sequence: MDVSKEAGHHANGFANGNTNGTTNGHTNGHTNAHTNVHTNVHTNGHANGHTKVHTNGNTNGTANETANEATNRTPNATSTTTTTFEGQLPQVPVAICGIGVRLPGGVRSDSDLYQMLVEKRDARAIVPADRYNIKSYYDPRGRPGSILTEYGYYIDEDLAQMDASMFSMSNVELSMMDPAQRLLLEVTREAFEGAGEGDFRGKNIGTFVGDFTTDWQELQYADLIHTAPYQVIGGSDFVLSNRLAYEYNLTGPSASIKTACSATAEALHEALLAIRAGSCPSAIVAGANLILTPRGGIGMTAMGVLSPDGSCKTFDSSANGFARGDSVCAIYIKRLDLALRDGNPIRAVIRACDSNADGGGTGRTFGTPNPITHEALIRKTYADAGLELHNTSVIECHGTGTPIGDPLEAEAVANCFADGKRPVYIGSVKPNLGHGEGGSAMASIIKAVVALENRTIIPNVKFKNPNPKIAWDKNLKVPTEPLPWPQDCQERMSINSFGLGGSNTHIIIDSAASFGIPSPHSSLHETADLSNEAQTSILLMSANSLSSITAMSQRYSEYVQAHPDRVEDMAYTLATRRERLKQASYCIFNDGVLSTPPPPVVSSGIVQTAFIFTGQGAQWLGMGKELMQQQRAFAHSIREMDAVIKSLEYAPDWSLEDSDADKSALAQTDRAQPISTALQVALVDLLATWNVHPAAVVGHSSGEVAAAYAARILTRREAIITAFYRGHACARCEIPGGMAAVGLGRTKVEPLLKSGVVIACENSNASVTISGDRDALEEAMAGLREKYPTTLVRKLQVPMGYHSHHMATVADLYHRLVSPHLDPKSPQVPYFSTVYGRQVQEAKAFGPSYWQLNMESPVLFRTAVSEMLREMGSNTAHLEVGPHSALAGPLRQIYEETGLSAPYASTMVRGQNSCTAFLEGIGKLFCFGLSPQIPSSKTRTVLPDIPTYPWDYKDKFWSETRVMSNWRFKKHRTHELLGERSLESSDIEPCWRNLLRTGTVPWLADHCVGSDIIFPAAGFIAMAGAAASQLAGSDGHYTVREVHIFSALVLHETTATELITTLRKQPLTSSLQSKWFEFSISSESNGVWTKYCSGLVTASVVTSAGLPEMPDTTAFSRKVDTSRWYTSMSRIGLNYGRRFVGLEDISCSPVHQVASVQINDVQDDYEPYPLHPSTIDKFLQSWTLAFTKGEYRLLTQLYLPTFIEELSVAPAPGKKISGRTLASGIPGTTVGSSLGVVDDELVLSLRGFKCKKTDDAFIQNVSKPRSMTLEWHLDTNFTDLHQLIKPTRDTAPENEILERLYVLYALENWDQLKNSTSSHPHLNIYLSWLEEEVKGFTEPGHPLISDSKELVSMDVPHRRREIAFLRQRSKHYPMAAAVEVYARTCARMVEIMEGKDNLLNVLLEGDLLAKFYNYYNDASDLSSFFQAAGLNKPHMRVLEIGAGTGGWTAHALRGLTSELGDRLYEEYTITDVSHGFLNQCKERFAAHSNIKYALLDISSDPLEQGFEEGYYDIVIASNLVETLCRCRKVLNPAGCLLIQEACAPGSRHGYIMGLFEGWWAGREDGRVRSPLIPVEEWDARLKLAGFEGAGTVVLDGQVPYYNYANIIARPAPTTIAQPESRLTLMTSSPELEDFSAILKTMLEEAGYLLDVCPWGADLPSDQDVVFLVDTEASVPVLADENPDNLATFLRYMKDISTSTVLWVTKPAQTICPDPRHGLITGMARTLRAELDMYIATLEIHKLDKPAASAVVQVLRKLQDAARLEESQGDEKSSDIKVDFEYAFSNGELLIPRFHPFVVDQVLLKDVPCADSRHLEIAQRGMLNTLHWVGDTLPELGPSEVELNMTAVGMNFLDLAVAMNIVDMAQSLGKGYNALGSEGSGIVTRVGSSVTNLKVGDRVATMGVDTSVFASKLQRPAESCVRLPPGLSDEDAAGILVPYATVLWSFIEKARLKKGQTVLIHSAAGGVGIAAIHVARWIGAEIYTTVGAQAKVDFLVNELDVPRDRIFHSRDDSFVKDVLSATNGKGIDVVLNSLSGELLHATWQCVAPGGCMLEIGKRDFLGRAQLAMHLFEENRAYFGIDLSRLALSEPEALQELLQKTMVLLEKQQLQPLWPTNTFDAVAVEDAFRYMQRGVHMGRIVVRMPEDDSVLPIAPVLPEPQFKADSTYLLTGGMGGLGRSIIRWMVSYGAKDITVMSRSAGNRDVDRALIAEIGELGCTLQCFAADIADMHSLQNVLSSLSKPVAGVLHMAMVLRDVGTLNMDFDSWTAALRPKVQGTWNLHDKLSENLDFFVLFSSISGTLGSYGQANYAAGNTFLDSFVRFRHGLGRPASVIDIAAIGDVGYVAETKDVAERIGRAFGSLGTEQEFLDTLQLAIARSTGPPEQQELSSKKTTKYAQPSQIVMHNRMIPPLSDPRNTTPWKNDARMAIYRNTEEAPQSTSSQSKERLGLFLVSLTTDPDQLDEPETPIIFAQEIAKRVAAFLMKGDKEDNALDTSLTLSQMGADSLVAIEIRNWWKQTFGMEISTLELNSPGQTFDSLGRLATKRLKEAYILKSS
What is the function of this protein?
Highly reducing polyketide synthase (HR-PKS); part of the gene cluster that mediates the biosynthesis of squalestatin S1 (SQS1, also known as zaragozic acid A), a heavily oxidized fungal polyketide that offers potent cholesterol lowering activity by targeting squalene synthase (SS) (PubMed:28605916).  SQS1 is composed of a 2,8-dioxobicyclic[3. 2. 1]octane-3,4,5-tricarboxyclic acid core that is connected to two lipophilic polyketide arms (PubMed:28605916).  These initial steps feature the priming of an unusual benzoic acid starter unit onto the highly reducing polyketide synthase clz14, followed by oxaloacetate extension and product release to generate a tricarboxylic acid containing product (PubMed:28605916).  The phenylalanine ammonia lyase (PAL) clz10 and the acyl-CoA ligase clz12 are involved in transforming phenylalanine into benzoyl-CoA (PubMed:28605916).  The citrate synthase-like protein clz17 is involved in connecting the C-alpha-carbons of the hexaketide chain and oxaloacetate to afford the tricarboxylic acid unit (PubMed:28605916).  The potential hydrolytic enzymes, clz11 and clz13, are in close proximity to pks2 and may participate in product release (PubMed:28605916).  On the other side, the tetraketide arm is synthesized by a the squalestatin tetraketide synthase clz2 and enzymatically esterified to the core in the last biosynthetic step, by the acetyltransferase clz6 (By similarity).  The biosynthesis of the tetraketide must involve 3 rounds of chain extension (By similarity).  After the first and second rounds methyl-transfer occurs, and in all rounds of extension the ketoreductase and dehydratase are active (By similarity).  The enoyl reductase and C-MeT of clz2 are not active in the final round of extension (By similarity).  The acetyltransferase clz6 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins (By similarity).  The biosynthesis of SQS1 requires several oxidative steps likely performed by oxidoreductases clz3, clz15 and clz16 (Probable).  Finally, in support of the identification of the cluster as being responsible for SQS1 production, the cluster contains a gene encoding a putative squalene synthase (SS) clz20, suggesting a likely mechanism for self-resistance (Probable).
What are the official names of this protein?
Squalestatin hexaketide synthase clz14, SQHKS clz14, Highly reducing polyketide synthase clz14, HR-PKS clz14, Squalestatin S1 biosynthesis cluster protein clz14, Zaragozic acid A biosynthesis cluster protein 14, Zaragozic acid A hexaketide synthase clz14.