Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone) (PubMed:18512859, PubMed:19437523). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide. 5 (S)-methylmalonyl-CoA + 11 H(+) + malonyl-CoA + 5 NADPH = 10-deoxymethynolide + 6 CO2 + 6 CoA + 2 H2O + 5 NADP(+) 6 (S)-methylmalonyl-CoA + 12 H(+) + malonyl-CoA + 5 NADPH = 7 CO2 + 7 CoA + 2 H2O + 5 NADP(+) + narbonolide Binds 3 phosphopantetheines covalently. Antibiotic biosynthesis. Homodimer (By similarity). Pikromycin PKS consists of a combination of multimodular (PikAI and PikAII) and monomodular (PikAIII and PikAIV) polypeptides each coding for a functional synthase subunit which participates in 1 (monomodular) or 2 (multimodular) of the six FAS-like elongation steps required for formation of the polyketide. Module 1, 2, 3, 4, 5, and 6 participating in biosynthesis steps 1, 2, 3, 4, 5, and 6, respectively. Cells lacking this gene are unable to produce methymycin, neomethymycin, narbomycin and pikromycin. Type I modular polyketide synthases (PKSs) catalyze the step-wise condensation of simple carboxylic acid derivatives. Organizationally, type I PKSs are arranged into modules, wherein each module is comprised of a set of catalytic activities that is responsible for a single elongation of the polyketide chain and the appropriate reductive processing of the beta-keto functionality. A minimal elongation module contains an acyl transferase (AT) domain, an acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The AT domain is responsible for loading the methylmalonyl-CoA extender unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS domain decarboxylates and then condenses the ACP-bound extender unit with the growing polyketide chain obtained from the preceding module to yield an ACP-bound beta-ketoacyl intermediate. In addition to the three core domains, each elongation module may contain up to three additional domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase (ER) that are responsible for the reductive processing of the beta-keto functionality prior to the next extension step. The presence of a KR domain alone gives rise to a beta-hydroxyl functionality, the presence of both a KR and a DH domain generates an alkene, while the combination of KR, DH, and ER results in complete reduction to the alkane. Finally, a thioesterase (TE) domain, typically found at the terminus of the last elongation module, catalyzes the termination of polyketide biosynthesis. The activity of this domain results in cleavage of the acyl chain from the adjacent ACP and formation of the macrocyclic ring.