Polyketide synthases (PKSs) are modular enzymes with exceptional potential as biocatalysts for producing non-native compounds. Here, we report the first PKS-based pathway for adipic acid (AA), an industrial monomer for nylon production, by engineering one of the most extensively hybridized PKS systems to date. Using a retrobiosynthetic approach, we identified EtnB, a succinyl-CoA loading module that uniquely retains the terminal carboxyl group, enabling access to dicarboxylic polyketide products, rarely produced by canonical PKSs. EtnB was coupled to a fully reducing extension module through an engineered communication linker, which improved ACP–KS interactions, enhanced titers, and demonstrated selective S-CoA loading in vivo. This construct integrates genes from five organisms, seven PKS modules joined across six non-natural junctions, and functions in both Escherichia coli and Pseudomonas putida. Additional engineering that included AT domain swaps, optimization of extender unit supply, and host strain metabolic rewiring further improved AA titers into the low mg/L range. Together, this work demonstrates that highly chimeric PKSs can be rendered functional through rational design, expands the PKS toolkit with a carboxyl-retaining loading module, and establishes a versatile platform for engineering diacids and other non-canonical products through PKS pathways.