Calcium Dependent Antibiotic (CDA), is a nonribosomal lipopeptide antibiotic from Streptomyces coelicolor. It is an undecapeptide with an unusual N-terminal 2,3-epoxyhexanoyl fatty acid side chain. It contains many nonproteinogenic amino acids such as D-4-hydroxyphenylglycine, D-3-phosphohydroxyasparagien, L-3-methylglutamic acid and Z-2,3-dehydrotryptophan. CDA is very similar in structure to the antibiotic daptomycin, which under the trade name Cubicin has recently been approved for the treatment of skin infections. The work described in this thesis focuses on a number of different areas, with the overall aim of delineating the biosynthetic origin of CDA and investigating the possibility of producing modified cyclic lipopeptides through a combined chemical and biochemical approach. Strategies used in engineering the biosynthesis of CDA may then be applied to other related, nonribosomal peptides of therapeutic importance, in order to improve their biological activity.