Expanding the Toolbox for Inducible Protein Expression With Automation‐enabled Generation of Glycomimetics

Inducible protein expression is a cornerstone of many aspects of industrial and molecular biotechnological processes. However, limited availability of inducible transcription factors can reduce our ability to control expression at a population level. The design and synthesis of a powerful inducer containing a fucose is demonstrated to induce protein expression through the lac operon only in cells with the ability to selectively de-fucosylate them. Batch and automated continuous-flow processes are reported for the syntheses of both 2'-fucosyl isopropyl-β-D-thiogalactopyranose (2'F-IPTG) and isobutyl-C-galactoside (2'F-IBCG) mimics. Fucosylation of the inducer allowed for fucosidase-dependent expression of a reporter protein, providing an additional layer of control over inducible gene expression.