Figure 2.

Structures of S atom replaced crypto-C8-actACP (4a). In this design, select carbonyl groups are replaced by S atoms, therein reducing number of potential Aldol/Claisen condensations. Access to 4a was achieved by chemoenzymatic conversion of mimetic 11 to its corresponding CoA analog by the action of three E. coli enzymes CoaA, CoaD, CoaE followed by loading on the actACP by Sfp (see Supporting Information).¹⁰⁻¹² Mimetics 12 and 13 and their corresponding crypto-loaded ACPs were not achieved due to instability. While the installation of the thioethers in 12 and 13 eliminated select Aldol/Claisen condensations, it did not ablate it. Ketide units are denoted by bars and are colored according to replacement of the carbonyl group with S atom (blue).