Biosynthesis of Bioactive Natural Products Derived from Theonellidae Family Marine Sponges

Marine sponges are among the most primitive animals and often contain unique, biologically active com-pounds. Several of these compounds have played an important roles as pharmaceutical leads for anti-cancer drugs, such as halichondrin B, which led to the development of an anti-breast cancer drug. Some compounds with remarkable biological activities are accumulated in significantly high concentrations in the sponge. How and why the marine sponges produce and accumulate bioactive natural products are long-standing ques-tions with both biochemical and ecological implications, since in sponges, the animal-microbe symbioses are presumed to be responsible for the biosynthetic machinery, consisting of efficient enzymes and regulatory systems for the specific biological activities of medicinally relevant natural products. In this review, I focus on the chemically rich Theonellidae family sponges and discuss the biosynthesis of bioactive peptides and polyketides. In particular, the biosynthetic pathway of calyculin A suggests that crosstalk between the sponge host and bacterial symbiont confers a chemical defense system on the immobile animal-microbe holobiont.