Using genomics to deliver natural products from symbiotic bacteria

Abstract

The availability of some natural products with promising anticancer activity has been limited because they are synthesized by symbiotic bacteria associated with specific animals. Recent research has identified the clusters of bacterial genes responsible for their synthesis, so that the molecules can be synthesized in alternative, easily cultured bacteria.

Figure 1

Structures of the main natural products discussed in this article. (a) Representative molecules that were originally isolated from beetles (pederin) or sponges (theopederin A and mycalamide A). They are biosynthesized by an uncultured symbiotic bacterium, most likely a Pseudomonas species, in both animal species. (b) Representative patellamide molecules that were originally isolated from ascidians. The amino acids from which each part of patellamide A are derived are indicated. They are made by Prochloron didemni, a cultured and genome-sequenced symbiotic cyanobacterium.

Figure 2

The two approaches discussed in this article for identifying the biosynthetic pathway of patellamide and expressing it in an alternative host bacterium. (a) Schmidt and colleagues [5] used an approach of complete genome sequencing, followed by sequence analysis to identify the biosynthetic pathway, cloning of the pathway into a heterologous host, and isolating the small molecule. (b) Jaspars and colleagues [6] used shotgun cloning of genomic DNA followed by screening of the resulting clone library for patellamide production. These steps could, in principle, be followed by sequencing the pathway, a step not reported by Jaspars and colleagues [6].