Supplementary Figure 2: Comparison of primers, extender units, pathway intermediates, enzymes, and products of (a) orthogonal iterative platform proposed and demonstrated in this study and (b) engineered reversal of β-oxidation1.
The ability of thiolases and β-reduction enzymes to function in an iterative fashion with functionalized substrates had not been demonstrated to date. The generation of these functionalized intermediates dictates the operation of the proposed platform with non-physiological intermediates that are not part of the host anabolic network and enables this orthogonal, iterative platform to facilitate the combinatorial synthesis of functionally diverse small molecules previously inaccessible by other pathways based on non-decarboxylative Claisen condensations, such as the β-oxidation reversal. Products shown are those demonstrated from the acyl-CoA node in each case, with product synthesis from additional pathway nodes also valid (See text and Figure 1b for details of all products produced in this study). In the structures of intermediate nodes, functional groups from primers are displayed in red and functional groups from extender units are displayed in blue. n represents the chain length of products.
