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Toward this goal, we have engineered commensal <jats:italic>E. coli<\/jats:italic> that selectively synthesize and secrete a model biotherapeutic in the presence of nitric oxide (NO), an intestinal biomarker for Crohn's disease (CD). This is accomplished by co\u2010expressing the pore forming protein TolAIII with the biologic, granulocyte macrophage\u2010colony stimulating factor (GM\u2010CSF). We have additionally engineered these bacteria to accumulate at sites of elevated NO by engineering their motility circuits and controlling pseudotaxis. Importantly, because we have focused on <jats:italic>in vitro<\/jats:italic> test beds, motility and biotherapeutics production are spatiotemporally characterized. Together, the targeted recognition, synthesis, and biomolecule delivery comprises a \u201csmart\u201d probiotics platform that may have utility in the treatment of CD. 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