penultimate amino acid, 3-methyl-glutamic acid (3mglu12), and the last amino acid, kyn13, into the chain. this exchange was achieved without engineering the interpeptide docking sites. these whole-subunit exchanges have been coupled 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 70 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 fermentation techniques. only a small percentage of the possible combinations of amino acids within the peptide core have been investigated thus far. history daptomycin, originally designated as ly 146032, was discovered by researchers at eli lilly and company in the late 1980s from the actinomycete streptomyces roseosporus. ly 146032 showed promise in phase i/ii clinical trials for treatment of infection caused by gram-positive organisms. lilly ceased development because high-dose therapy was associated with adverse effects on skeletal muscle, including myalgia. the rights to ly 146032 were acquired by cubist pharmaceuticals in 1997, which following u.s. food and drug administration (fda) approval in september 2003, for use in people older than 18 years, began marketing the drug under the trade name cubicin. cubicin is marketed in the eu and in several other countries by novartis following its purchase of chiron corporation, the previous licensee.