Spongosine production from a Tectitethya crypta-associated microorganism, Vibrio harveyii

Spongothymidine (Ara T), spongouridine (Ara U), and spongosine were isolated from the Caribbean sponge Tectitethya crypta in the early 1950s and given the general name ‘spongonucleosides’. Spongothymidine and spongouridine differed from known nucleosides by the replacement of ribose with arabinose, the C-2 epimeric sugar. These discoveries led to the development of synthetic arabinoside derivatives of cytosine (Ara C) and adenosine (Ara A) in 1959 and 1960, respectively. Ara C (cytarabine) is currently used as a chemotherapeutic agent for Hodgkin’s lymphoma and acute myelocytic leukemia whereas Ara A is used as an antiviral agent. In contrast, spongosine has demonstrated a diverse bioactivity profile including anti-inflammatory activity, analgesic and vasodilation properties. Investigations into unusual nucleoside production by T. crypta-associated microorganisms using mass spectrometric and spectroscopic techniques has identified a spongosine-producing strain of Vibrio harveyi and several structurally related compounds from multiple strains. These results support a microbial source for the unusual nucleosides originally found in this marine invertebrate, and fermentation of these strains may abrogate the need for sponge collection to acquire these valuable metabolites.