Metabolic engineers use technology and ways of thinking from traditional science and engineering disciplines as well as the emergent field of synthetic biology to genetically manipulate cellular metabolic pathways for applications in medicine, energy, the environment, and more. Two important challenges to successful metabolic engineering are how to optimize the metabolic output and how to make products that are toxic to cells. Our research addressed these challenges with the development of a new strategy for the selection of optimal genotypes for enzyme production and the use of microfluidic droplets for cell-free protein synthesis. We focused on a prototype metabolic reaction by which caffeine demethylase converts caffeine into theophylline, and used a ribozyme-riboswitch that cleaves itself upon binding theophylline as the basis for selection of genetic regulatory elements that most efficiently produce caffeine demethylase.