The majority of natural product biosynthetic gene clusters in bacteria are silent under standardlaboratory growth conditions,m aking it challenging to uncover any antibiotics that they may encode.Herein, bioactivity assays are combined with high-throughput elicitor screening (HiTES) to access cryptic, bioactive metabolites.A pplication of this strategy in Saccharopolyspora cebuensis,w ith inhibition of Escherichia coli growth as ar ead-out, led to the identification of an ovel lanthipeptide,c ebulantin. Extensive NMR spectroscopic analysis allowed the elucidation of the structure of cebulantin. Subsequent bioactivity assays revealed it to be an antibiotic selective for Gram-negative bacteria, especially against Vibrio species.T his approach, referred to as bioactivity-HiTES,h as the potential to uncover cryptic metabolites with desired biological activities that are hidden in microbial genomes.