In this study we report on the genomics-guided exploration of the metabolic potential of the newly discovered strain Kitasatospora sp. HKI 714. The bioinformatics analysis of the whole genome sequence revealed the presence of a biosynthetic gene cluster presumably responsible for the biosynthesis of formerly unknown endophenazine derivatives. A 200 L cultivation combined with bioactivity-guided isolation techniques revealed four new natural products belonging to the endophenazines and the 5,10-dihydrophenazines. Detailed descriptions of their biological effects, mainly focused on antimicrobial properties against several mycobacteria, are given.