Here, we report the discovery and structural elucidation of myxoprincomide (1), a novel NRPS/PKS natural product from Myxococcus xanthus DK1622, by combining methods of targeted mutagenesis, liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), and statistical data evaluation (Figure 1). Myxoprincomide (1), a linear peptide bearing some unusual residues, is produced by the NRPS/PKS biosynthetic machinery encoded by the mxp (MXAN_3779) gene locus. Moreover, by correlating additional very-low-abundance natural products to biosynthetic pathways in DK1622 we demonstrate how a comprehensive metabolome-mining approach can complement genome-mining strategies in the discovery of secondary metabolites.