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 lead compound for the treatment of hyper-cholesterolemia by targeting squalene synthase (SS) (PubMed:15489970). Pks1 is responsible for the biosynthesis of the tetraketide sidechain of SQS1 (PubMed:15489970). The biosynthesis must involve 3 rounds of chain extension. After the first and second rounds methyl-transfer occurs, and in all rounds of extension the ketoreductase and dehydratase are active. The enoyl reductase and C-MeT are not active in the final round of extension (PubMed:15489970). Secondary metabolite biosynthesis. Multidomain protein; including 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 dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (CMeT) domain responsible for the incorporation of methyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm.