ABSTRACT
Bioactive natural products have long been studied for their pharmaceutical potential and/or their ecological relevance. The marine bryozoan, Bugula neritina, is the source of bryostatins, macrocyclic polyketides with anticancer, anti-Alzheimer's disease, and anti-HIV activity. These compounds are produced by a symbiotic bacterium found in all life stages of B. neritina. Bryostatins have also been shown to be ecologically relevant as they are unpalatable and protect the host larvae from predators, resulting in a tritrophic interaction between a bacterial symbiont, the host, and host predators. While the symbiont-produced bryostatins contribute to host defense, the absence of the symbiont in some colonies reduces their fecundity, suggesting that the bryostatins may also play a role in host physiology. Bryostatins target eukaryotic protein kinase C (PKC), and the amino acid binding residues of the bryostatin binding region of PKC in B. neritina differ compared to that of mammalian PKC. It is hypothesized that these differences may affect bryostatin binding affinity, which could modulate PKC activity. The presence of related symbionts, some that produce bryostatins and some that do not, in other bugulid species presents a complex system in which host/symbiont and symbiont-produced natural product coevolution should be further investigated.
