New derivatives of daptomycin (Figure 9) were originally generated by exchanging the third NRPS subunit (DptD) with the terminal subunits from the A54145 (Factor B1) or calcium-dependent antibiotic (CDA) pathways to create molecules containing Trp13, Ile13, or Val13. Dpt D is responsible for incorporating the penultimate amino acid, 3-methyl-glutamic acid (3mGlu12), and the last amino acid, kynurenine (Kyn13), into the growing chain. This exchange was achieved without engineering the interpeptide dockingsites. These whole-subunit exchanges have been coupled combinatorially with the deletion of the Glu12-methyltransferase gene, with module exchanges at intradomain linker sites at Ala8 and Ser11, and with variations of natural fatty acid side chains to generate over seventy novel lipopeptides in significant quantities; most of these resultant lipopeptides have potent antibacterial activities. Some of these compounds have in vitro antibacterial activities analogous to daptomycin. Further, one displayed ameliorated activity against an "E. coli" imp mutant that was defective in its ability to assemble its inherent lipopolysaccharide. A number of these compounds were produced in yields that spanned from 100 to 250 mg/liter; this, of course, opens up the possibility for successful scale-ups by means of fermentation techniques. Only a small percentage of the possible combinations of amino acids within the peptide core have been investigated thus far.