We present a high throughput micro-droplet based method for directed evolution of yeast cell factories for improved production of industrial enzymes. The workflow includes a fluorescently activated droplet sorter which was found to accurately sort droplets with a false positive rate of 0.0002 at 300 Hz. The workflow was used to screen a library of α-amylase expressing yeast mutants. A candidate yeast strain with a more than twofold increase in α-amylase production was isolated from a single round of directed evolution