We have been engaged in metagenomic comparison of secondary metabolite biosynthetic pathways in symbiotic bacteria from marine animals known as ascidians. Exploration of these pathways has been useful for biotechnology, enabling synthesis of new compounds using genetic engineering. In addition, comparison of closely related biosynthetic enzymes from these symbioses has provided an unprecedented view of enzyme evolution and function. New insights into peptide circularization and heterocyclization will be discussed.