Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of cladosporin, a tricyclic octaketide that acts as an antimalarial agent though inhibition of the Plasmodium falciparum lysyl-tRNA synthetase (PubMed:26783060). The highly reducing polyketide synthase cla2 is responsible for biosynthesis up to the pentaketide stage, including of the tetrahydropyran (THP) ring, whereas the three subsequent ketide extensions with no reduction are catalyzed by the non-reducing polyketide synthase cla3 (PubMed:26783060). Secondary metabolite biosynthesis. 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). The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-ter of the protein (By similarity). Cladosporin has been intensely studied for its antimalarial activity though inhibition of the Plasmodium falciparum lysyl-tRNA synthetase (PubMed:22704625, PubMed:24935905, PubMed:26074468). Cladosporin has also antifungal activity against dermatophytes, as well as Penicillium and Aspergillus species (PubMed:5169000).