Pharmaceutically important polyketides are produced during the stationary phase of growth of Streptomyces species in fermenters. The source of intracellular metabolites that are funneled into polyketide biosynthesis has proven elusive. We uncover the mystery and devised a titer improvement strategy.

Using a FokI fusion design, we show that Type I CRISPR-Cas systems can be expressed, reconstituted, and faithfully trafficked to the nucleus for genome engineering in human cells