Trading molecules and tracking targets in symbiotic interactions

Abstract

It is probable that nearly every natural product structure results from interactions between organisms. Symbiosis, a subset of inter-organism interactions involving closely associated partners, has recently provided new and interesting experimental systems for the study of these interactions. This review discusses new observations about natural product function and structural evolution that emerge from the study of symbiotic systems. In particular, these advances directly address long-standing 'how' and 'why' questions about natural products, providing fundamental insights about the evolution, origin and purpose of natural products that are inaccessible by other methods.

Figure 1

Roles of metabolism in symbiosis. Macroorganisms such as this ascidian animal (center) share metabolic products with symbiotic microbes such as Prochloron bacteria (left and right). In return, bacteria can provide metabolic intermediates back to hosts (left) or they can synthesize natural products that have many different possible roles, including aiding in predation, chemical defense, or antibiosis. Many other roles are possible, and no roles for natural products have yet been experimentally determined for the symbiosis shown. Ascidian photo: Chris Ireland. Prochloron photo: Mohamed Donia.

Figure 2

Biosynthesis of a stilbene by a nematode symbiont.

Figure 3

Bryostatins and ‘E. sertula’ are found throughout the tissues of the host animal, B. neritina. The structure of bryostatin is shown, as well as a series of confocal images of B. neritina larvae. The location of bryostatins is indicated in blue, while ‘E. sertula’ is labeled with a fluorescent yellow probe. (Photo kindly provided by Koty Sharp.)

Figure 4

Evolution of natural product pathways. (a) Pederin and onnamide. Putative PKS in black, interrupting oxidase in green. The pederin cluster contains an interrupting oxidase, without which it would produce an onnamide-like structure. (b) Ascidian compounds, patellamides and relatives. Putative enzymes in black, precursor peptides in red. Variants of the patellamide pathway (top) are virtually 100% identical except in small segments that directly encode the resulting patellamide products. The same pattern is seen in variants of the trunkamide pathway (bottom). These pathways are >97% identical at the DNA level except in a small region marked by a blue box. Differences in heterocyclization versus prenylation of serine and threonine can be explained by the sequence difference within this blue box.

Figure 5

Potential co-evolution of sponge symbionts and natural products. A 16S rRNA tree was derived for the sponge-specific filamentous bacterial group, ‘Candidatus Entotheonella palauensis’. The symbionts are delta-proteobacteria the branch closely with the myxobacteria (upper left) and sulfate reducers (lower left). ‘E. palauensis’ sequences were obtained from individual sponges and compared with natural products isolated from those same sponges. Filamentous ‘E. palauensis’ hybridized to a specific fluorescent probe are shown at center. Adapted from a figure first printed in Marine Biology, reprinted with permission.