Biodiversity, chemical diversity and drug discovery.
Drugs developed from microbial natural products are in the fundaments of modern pharmaceutical companies. Despite decades of research, all evidences suggest that there must remain many interesting natural molecules with potential therapeutic application yet to be discovered. Any efforts to successfully exploit the chemical diversity of microbial secondary metabolites need to rely heavily on a good understanding of microbial diversity, being the working hypothesis that maximizing biological diversity is the key strategy to maximizing chemical diversity. This chapter presents an overview of diverse topics related with this basic principle, always in relation with the discovery of novel secondary metabolites. The types of microorganisms more frequently used for natural products discovery are briefly reviewed, as well as the differences between terrestrial and marine habitats as sources of bioactive secondary metabolite producers. The concepts about microbial diversity as applied to prokaryotes have evolved in the last years, but recent data suggest the existence of true biogeographic patterns of bacterial diversity, which are also discussed. Special attention is dedicated to the existing strategies to exploit the microbial diversity that is not easy to tackle by conventional approaches. This refers explicitly to the current attempts to isolate and cultivate the previously uncultured bacteria, including the application of high throughput techniques. Likewise, the advances of microbial molecular biology has allowed the development of metagenomic approaches, i.e., the expression of biosynthetic pathways directly obtained from environmental DNA and cloned in a suitable host, as another way of accessing microbial genetic resources. Also, approaches relying on the genomics of metabolite producers are reviewed.
Singh
Sheo B
SB
Merck Research Laboratories, Rahway, New Jersey 07065, USA. Sheo_singh@merck.com
Pelaez
Fernando
F
D001419:Bacteria / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001431:Bacteriological Techniques; D044822:Biodiversity; D001685:Biological Factors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003001:Cloning, Molecular; D015195:Drug Design; D016680:Genome, Bacterial; D007218:Industrial Microbiology / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000235:genetics; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012988:Soil Microbiology; D013329:Structure-Activity Relationship; D014871:Water Microbiology
D001685:Biological Factors; D004364:Pharmaceutical Preparations