Synthetic biology is revolutionizing the way in which the biosphere is explored for natural products. Through computational genome mining, thousands of biosynthetic gene clusters are being identified in microbial genomes, which constitute a rich source of potential novel pharmaceuticals. New methods are currently being devised to prioritize these gene clusters in terms of their potential for yielding biochemical novelty. High-potential gene clusters from any biological source can then be activated by ‘refactoring’ their native regulatory machinery, replacing it by synthetic, orthogonal regulation and optimizing enzyme expression to function effectively in an industry-compatible target host. Various part libraries and assembly technologies have recently been developed which facilitate this process.