Streptomyces coelicolorM145 is a model strain extensively studied to elucidate the regulation of antibiotic biosynthesis inStreptomycesspecies. This strain abundantly produces the blue polyketide antibiotic, actinorhodin (ACT), and has a low lipid content. In a process designed to delete the gene encoding the isocitrate lyase (sco0982) of the glyoxylate cycle, an unexpected variant ofS. coelicolorwas obtained besidesbona fide sco0982deletion mutants. This variant produces 7- to 15-fold less ACT and has a 3-fold higher triacylglycerol and phosphatidylethanolamine content than the original strain. The genome of this variant was sequenced and revealed that 704 genes were deleted (9% of total number of genes) through deletions of various sizes accompanied by the massive loss of mobile genetic elements. Some deletions include genes whose absence could be related to the high total lipid content of this variant such as those encoding enzymes of the TCA and glyoxylate cycles, enzymes involved in nitrogen assimilation as well as enzymes belonging to some polyketide and possibly trehalose biosynthetic pathways. The characteristics of this deleted variant ofS. coelicolorare consistent with the existence of the previously reported negative correlation existing between lipid content and antibiotic production inStreptomycesspecies.