Identification of the putative bryostatin polyketide synthase gene cluster from "Candidatus Endobugula sertula", the uncultivated microbial symbiont of the marine bryozoan Bugula neritina.

The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium "Candidatus Endobugula sertula" ("E. sertula").

bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina.

"Candidatus Endobugula sertula," the uncultivated bacterial symbiont of Bugula neritina, is the proposed source of the bryostatin family of anticancer compounds. We cloned a large modular polyketide synthase (PKS) gene complex from "Candidatus Endobugula sertula" and characterized one gene, bryA, which we propose is responsible for the initial steps of bryostatin biosynthesis. Typical PKS domains are present.

Approaches to identify, clone, and express symbiont bioactive metabolite genes.

This review discusses approaches to identify, clone, and express bioactive metabolite genes from symbionts of marine invertebrates. Criteria for proving symbiotic origin of bioactive metabolites are presented, followed by a comprehensive, practically-oriented overview of techniques to be applied. The Bugula neritina/Endobugula sertula association is used as a primary example, but other symbioses are discussed.