Emerging concepts promising new horizons for marine biodiscovery and synthetic biology

Abstract

The vast oceans of the world, which comprise a huge variety of unique ecosystems, are emerging as a rich and relatively untapped source of novel bioactive compounds with invaluable biotechnological and pharmaceutical potential. Evidence accumulated over the last decade has revealed that the diversity of marine microorganisms is enormous with many thousands of bacterial species detected that were previously unknown. Associated with this diversity is the production of diverse repertoires of bioactive compounds ranging from peptides and enzymes to more complex secondary metabolites that have significant bioactivity and thus the potential to be exploited for innovative biotechnology. Here we review the discovery and functional potential of marine bioactive peptides such as lantibiotics, nanoantibiotics and peptidomimetics, which have received particular attention in recent years in light of their broad spectrum of bioactivity. The significance of marine peptides in cell-to-cell communication and how this may be exploited in the discovery of novel bioactivity is also explored. Finally, with the recent advances in bioinformatics and synthetic biology, it is becoming clear that the integration of these disciplines with genetic and biochemical characterization of the novel marine peptides, offers the most potential in the development of the next generation of societal solutions.

Keywords: lantibiotics; marine bioactives; mimetics; motif/domain; peptides; quorum quenching; quorum sensing; signaling molecules.

Figure 1

Biotechnology applications of marine peptides. The enormous potential for application of marine peptides has begun to be realized in recent years. Developments, both technological and societal, across a wide spectrum of industries have led to the use of peptides in previously unforeseen products. As technologies continue to develop, and pending our capacity to harvest the rich reservoirs of rare and novel bioactive peptides, the market need for these molecules is likely to continue its growth trajectory.

Figure 2

Marine biodiscovery pipeline for subtilomycin. The identification and isolation of novel bioactive compounds from the marine ecosystem requires the integration of several technologies. The cross-disciplinary nature of these pipelines merely reflects the complexity of the natural compounds that are produced by marine bacteria and other organisms. Produced by a marine sponge isolate that was found to produce an antimicrobial compound upon initial screening, isolation and characterization of the novel lantibiotic required the combination of chemical and genomic technologies. Subsequently, purified and characterized subtilomycin was found to have activity against a broad spectrum of Gram negative and Gram positive pathogens.

Figure 3

Marine metagenomics for bioactive peptide discovery. Overcoming the ‘great plate anomaly’ has proven difficult where marine organisms are concerned and many rare and potentially important bioactivities remain as yet out of reach. However, the advent of metagenomics based technologies has opened up new avenues for exploration and it provides us with a real opportunity to extract new potential from the marine environment. Bottlenecks remain, however, and these will need to be overcome before the full potential of marine biodiscovery can be realized. These include issues surrounding DNA extraction, sequencing depth, heterologous expression, standardization of technologies and metadata, and bioactive detection. Solving these limitations will require the integration of cross-disciplinary expertise backed by powerful data systems and industrial know how.