"streptomyces roseosporus",the producer organism of daptomycin,is amenable to genetic manipulation;the daptomycin biosynthetic gene cluster has been cloned,sequenced,and expressed in "s.lividans";the lipopeptide biosynthetic machinery has the potential to be interrupted by variations of natural precursors,as well as precursor-directed biosynthesis,gene deletion,genetic exchange,and module exchange;the molecular engineering tools have been developed to facilitate the expression of the three individual nrps genes from three different sites in the chromosome,using ermep*for expression of two genes from ectopic loci;other lipopeptide gene clusters,both related and unrelated to daptomycin,have been cloned and sequenced,thus providing genes and modules to allow the generation of hybrid molecules;derivatives can be afforded via chemoenzymatic synthesis;and lastly,efforts in medicinal chemistry are able to further modify these products of molecular engineering.