Highly reducing polyketide synthase (HR-PKS); part of the gene cluster that mediates the biosynthesis of phaeospelide A, a fungal polyene macrolide with a 34-membered macrolactone ring and an all-trans conjugated hexaene structure (PubMed:31180682). The HR-PKS ApmlA uses acetyl-CoA and malonyl-CoA as its starter and extender units, respectively, and provides the large carbon framework in phaeospelide via 16 cycles of polyketide chain elongation, which is the largest number identified in fungal iterative PKSs thus far (PubMed:31180682). During round 1, the KR domain reduces beta-ketone to an L-oriented hydroxy group, while during later rounds, it provides hydroxy groups in the D-configuration (PubMed:31180682). The characteristic conjugated hexaene moiety is built during the later rounds (10-15), when the KR and DH domains are at work but ER is off (PubMed:31180682). Phylogenetic analysis of the DH domain suggests that a polyene formation is programmed in the DH domain (PubMed:31180682). Finally, the mature ACP-tethered carbon chain is transferred to the serine residue of the thiohydrolase apmlB, followed by intramolecular macrolactonization, generating phaeospelide A (PubMed:31180682). When one elongation cycle during rounds 7-9 is skipped, phaeospelide B is biosynthesized instead (PubMed:31180682). Binds 1 phosphopantetheine covalently. 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; 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.