ABSTRACT
Since the golden era of antibiotics, natural products played an important role in the development of drugs (Hopwood, 2007a; Bérdy, 2005, 2012; Zotchev, 2012; Kurtböke et al., 2014; Müller and Wink, 2014). So far 63% of new drugs have been classied as naturally derived, including unmodied or modied natural products, or synthetic compounds deriving from the pharmacophore scaffolds of natural products (Imhoff et al., 2011). Continued mining of these known scaffolds has been an effective approach in delivering new drugs. Examples include exploitation of bioactive synthetic scaffolds like the oxazolidinones and diaminopyrimidines leading to the delivery of new compounds and proceeding into late-stage clinical trials (Imhoff et al., 2011). Eight quinolone and uoroquinolone derivatives were also introduced to the market through such approaches (Butler and Cooper, 2011; Wright, 2012), and 68% of antibiotics against bacterial, fungal, parasitic, and viral infections and 63% of drugs for cancer treatment introduced between 1981 and 2008 are derived from natural sources (Cragg et al., 2009; Imhoff et al., 2011). Interest in the discovery of unique pharmacophores expanded to marine environments when the rediscovery of the known compounds originating mostly from terrestrial microorganisms became an obstacle (Hopwood, 2007b; Zotchev, 2012). Stemming from the urgent current need for novel and potent therapeutic agents for the treatment of existing and emerging diseases and the increasing rate of recent marine-derived biodiscoveries supported the intensive
CONTENTS
9.1 Introduction ........................................................................................................................ 165 9.2 Marine Environments and Biodiscovery ....................................................................... 166
9.2.1 Marine Actinomycetes .......................................................................................... 167 9.2.1.1 Actinomycetes as Symbionts of Marine Macrofauna ........................ 168 9.2.1.2 Actinomycetes in Marine Sediments ................................................... 169
9.3 Metagenomics ..................................................................................................................... 170 9.3.1 Discovery of Novel Compounds via Metagenomical Approaches ................ 170
9.4 Hosts for the Heterologous Expression of Actinomycete-Derived Biosynthetic Gene Clusters...................................................................................................................... 174
9.5 Metagenomics-Based Insights into Biosynthetic Potential of Marine Actinomycetes ....175 9.6 Future Prospects ................................................................................................................ 176 Acknowledgments ...................................................................................................................... 177 References ..................................................................................................................................... 178
search for new substances from marine organisms, including marine actinomycetes (Molinski et al., 2009; Demain and Vaishnav, 2011; Imhoff et al., 2011; Schumacher et al., 2011; Zotchev, 2012; Kurtböke et al., 2014). Moreover, rapid progress in metagenomics has revealed the true extent of marine microbial, including actinobacterial, diversity via direct access to the genomes of numerous uncultivable microorganisms (Li and Qin, 2005).
