Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of chrodrimanin B, a meroterpenoid that acts as a potent blocker of insect GABA-gated chloride channels (PubMed:30417647). The first step of the pathway is the biosynthesis of 6-hydroxymellein by the polyketide synthase cdmE (PubMed:30417647). The prenyltransferase cdmH acts as a 6-hydroxymellein 5-farnesyltransferase and produces the hydrophobic metabolite verruculide C (PubMed:30417647). The FAD-dependent monooxygenase cdmI further converts verruculide C into verruculide B (PubMed:30417647). The terpene cyclase cdmG then produced the pentacyclic molecule 3-hydroxypentacecilide A, the backbone structure of chrodrimanin B, via folding the farnesyl moiety of the substrate into the chair-boat conformation (PubMed:30417647). The short-chain dehydrogenase/reductase cdmF functions as the 3-OH dehydrogenase that oxidizes the C-3 hydroxyl group of 3-hydroxypentacecilide A and produces chrodrimanin C, the dehydrogenated product of 3-hydroxypentacecilide A (PubMed:30417647). The cytochrome P450 monooxygenase cdmJ then accepts both 3-hydroxypentacecilide A and chrodrimanin C and functions as a C-7-beta-hydroxylase to produce respectively chrodrimanin H and chrodrimanin F (PubMed:30417647). The dioxygenase cdmA accepts chrodrimanin H to afford chrodrimanin E, which is further transformed to chrodrimanin A by the dioxygenase cdmD (PubMed:30417647). CdmA can also accept chrodrimanin C as substrate to convert it into verruculide A, which is further converted into chrodrimanin T by cdmD (PubMed:30417647). The last step of the biosynthesis is proposed to be performed by the acetyltransferase cdmC which acetylates chrodrimanin A to yield chrodrimanin B (Probable). The pathway may also lead to the production of additional shunt products, including chrodrimanins T and U (PubMed:30417647). AH2 + 5 H(+) + 5 malonyl-CoA = 6-hydroxymellein + A + 5 CO2 + 5 CoA + H2O Secondary metabolite biosynthesis; terpenoid 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 (Probable). The DH and CMeT domains are inactive due to mutations of their catalytic residues, as consistent with the required reactions to synthesize 6-hydroxymellein (Probable). The ER domain could be active, but it should not affect the PKS chemistry due to the inactive DH domain (Probable). Compounds in the chrodrimanin family such as chrodrimanin A or verruculide A exhibit strong inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and therefore, they could potentially be developed into drugs for the treatment of type 2 diabetes or obesity (PubMed:26115570). Furthermore, chrodrimanin B, the end product of the pathway involving chrodrimanin A or verruculide A, does not exhibit the PTP1B inhibitory activity, while it functions as a potent blocker of insect GABA-gated chloride channels (PubMed:25902139).