Technical Abstract: The manzamines are complex, polycyclic, marine derived alkaloids that are important as pharmaceutical agents due to their activity as antimalarial, antituberculosis, and antitumor drug-leads. In order to understand the metabolism and biogenesis of the manzamines, we examined the biotransformation of manzamine using a number of microorganisms. Our biotransformation studies have focused both on the improvement of the activity and reduced toxicity of the manzamines that may be generated by sponge-associated microbes. Biotransformation studies of 8-hydroxymanzamine A, manzamine F, and manzamine X showed that the biotransformation products generated in our laboratory are the same as further oxidized manzamine analogs isolated directly from the sponge.