We present a novel fully-automated droplet-based microfluidic system to enable programmable combinatorial mixing, electroporation for CRISPR-based gene editing, and high-throughput screening on chip. It is highly robust and compatible with conventional liquid handler systems to interface, enabling 100 different reactions at a time with dramatically lower reagents consumption. Utilizing proposed system, we perform accelerated optimization of biosynthetic pathway of indigoidine in Escherichia coli (E. coli).