The genus Salinispora is notable for its ability to produce a spectacular array of potent natural products. Total genome sequencing of two species, S. tropica and S. arenicola, revealed that these marine actinomycete bacteria dedicate a large percentage at 10-15% of its genomic capacity to the synthesis of natural products. This presentation will focus on the genomic mining of new chemical entities from Salinispora and the extension of its biosynthetic capacity to small molecules through genetic engineering of established pathways (i.e., salinosporamide, sporolide and cyclomarin).