Emerging Strategies and Integrated Systems Microbiology Technologies for Biodiscovery of Marine Bioactive Compounds

Abstract

Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, and halogenated functional groups) are frequently found in marine metabolites. These facts have resulted in the production of bioactive substances with different properties than those found in terrestrial habitats. In fact, the marine environment contains a relatively untapped reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics, combinatorial biosynthesis, synthetic biology, screening methods, expression systems, bioinformatics, and the ever increasing availability of sequenced genomes provides us with more opportunities than ever in the discovery of novel bioactive compounds and biocatalysts. The combination of these advanced techniques with traditional techniques, together with the use of dereplication strategies to eliminate known compounds, provides a powerful tool in the discovery of novel marine bioactive compounds. This review outlines and discusses the emerging strategies for the biodiscovery of these bioactive compounds.

An Overview on Marine Sponge-Symbiotic Bacteria as Unexhausted Sources for Natural Product Discovery

“…They also mimicked the inner structure of the sponge by applying floating polycarbonate filters to low nutrient media. Such an approach once again confirmed the use of alternative cultivation methods to culture previously uncultivated species [193].…”

“…Their approach combined with rational design of culturing methods revealed a large diversity of bacteria associated with this sponge, many of which were only distantly related to previously described bacteria [63]. Sipkema, et al [193] used the same approach and cultured 10-14% of the community of a Haliclona sponge, a higher cultivability rate than previously recorded for sponge-associated bacteria. They also mimicked the inner structure of the sponge by applying floating polycarbonate filters to low nutrient media.…”

“…The biosynthetic PKS and NRPS gene clusters also require specific induction in order to obtain a specific metabolite and without these inducing conditions, metabolites may be unexpressed [212,213], and even if the expression of a particular gene pathway is successful it may not produce the same or all of the expected metabolites [52,202]. Therefore, the use and development of alternative bacterial hosts for gene expression, alternative expression systems and multi-host shuttle vectors are required to overcome the metagenomics limitations [193]. …”

Natural Products as Pharmaceuticals and Sources for Lead Structures**Note: This chapter reflects the opinions of the authors, not necessarily those of the US Government

“…Finally, the paper by Rocha-Martin et al that was recently published gives an excellent overview of the manifold ways in which "systems biology" can be used to aid in the discovery of bioactive compounds from marine microbes [131]. …”

The marine biodiscovery pipeline and ocean medicines of tomorrow

“…However, notwithstanding these difficulties there has been a 'renaissance' in marine drug discovery in the last decade due to technological developments that have accelerated structural elucidation and screening, and the use of marine microbial genomics to provide biosynthetic pathways for the production of marine natural products (Glaser and Mayer, 2009). The development of emerging 'omics' tools such direct sequencing of eDNA, next generation sequencing technologies, metaproteomic and synthetic biology, heterologous expression and bioinformatic tools will improve the discovery and production of these compounds and facilitate the study of biosynthetic pathways of organisms previously inaccessible by traditional methods (see review by Rocha-Martin et al, 2014). This is coupled with the fact that alternative technologies such as combinatorial chemistry have failed to provide the pharmaceutical industry with the chemical diversity necessary to significantly increase the number of new drug-like leads.…”