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Introduction
Natural products have been an overwhelming success in our society. The use of plant and microbial secondary metabolites has aided in doubling of our life span in the 20th century. They have reduced pain and suffering, and revolutionized medicine by enabling the transplantation of organs. Since their chemical diversity is based on biological and geographical diversity, the entire globe is explored for bioprospecting by researchers. Researchers have had easy access to terrestrial life from which most of the pharmaceutically successful natural products originate. However, the ocean hosts a vast repertoire of life forms brimming with natural products of potential pharmaceutical importance. Marine bioprospecting is a relatively new phenomenon; thus, marine life is a relatively unexplored area of opportunity. New methods are being developed to grow the so‐called ‘unculturable’ microbes from both the soil and the sea. Most biologically active natural products are secondary metabolites with complex structures. In some cases, the natural product itself can be used, but in others, derivatives made chemically or biologically are the molecules used in medicine. Biosynthetic pathways are often genetically manipulated to yield the desired product. With the advent of combinatorial biosynthesis, thousands of new derivatives can now be made by this biological technique, which is complementary to combinatorial chemistry.
Secondary metabolism evolved in nature in response to needs and challenges of the natural environment. Nature has been continually carrying out its own version of combinatorial chemistry (Verdine, 1996) for over the three billion years in which bacteria have inhabited the earth (Holland, 1998). During that time, there has been an evolutionary process going on in which producers of secondary metabolites evolved according to their local environments. If the metabolites were useful to the producing species, the biosynthetic genes were retained and genetic modifications further improved the process. Combinatorial chemistry practised by nature is much more sophisticated than combinatorial chemistry in the laboratory, yielding exotic structures rich in stereochemistry, concatenated rings and reactive functional groups (Verdine, 1996). As a result, an amazing variety and number of products have been found in nature. This natural wealth is tapped for drug discovery using high‐throughput screening and fermentation, mining genomes for cryptic pathways, and combinatorial biosynthesis to generate new secondary metabolites related to existing pharmacophores....