Biotechnology is generally regarded as a key technology of the new century. The drivers of biotechnology are economic competitiveness, public demand, and radical technological innovation. The success of this technology is dependent on the discovery of novel chemicals, materials, and catalysts which, in the past, have been found as natural products through the application of traditional biological knowledge and procedures. Now, at the turn of the century, a paradigm shift driven by new technologies is occurring in the way we search for exploitable biology. This paradigm shift is exemplified by the extent of biodiversity now revealed and recognized by molecular biology, information and data-rich methods for characterizing organisms and for defining taxon-property relationships, high-throughput screening, the PCR and DNA sequencing, whole-genome sequencing and annotation, and functional genomics. In each of these areas, the rate at which data are being generated is increasing exponentially, leading to major issues on data management, data accessibility, and the derivation of useful knowledge. Bioinformatics has the potential to translate genomics data into knowledge. Currently bioinformatics is largely driven by the concerns of human medicine: the required information is on disease-related genes and on discovering targets to combat pathogens and dysfunctions. However, there are other areas of biotechnology in which bioinformatics can create useful information from genomics. As Rouzé (395) has pointed out, “This means that from the same genomics data, different information systems will have to be built, each domain bringing its own corpus of facts, concepts and analytical tools.” In order to realize this objective, the relationships between biological objects and phenomena will need to be recognized at a much more sophisticated level and in silico devices developed as discovery tools to generate biological hypotheses that can be tested experimentally.
The foregoing does not, however, imply that we can afford to neglect innovative biology, such as developing means to bring uncultivated microorganisms into laboratory culture. Similarly, the demand for antimicrobials and other biotherapeutic products is high, but the high-throughput screens now used in their discovery require pure compounds. In turn this requires optimization of microbial growth and expression, scale-up, and purification with a significant input of resources for each organism studied and, therefore, careful choice of organisms to screen. However, microorganisms are frequently poorly classified and identified and therefore may be difficult to choose on a completely rational basis. Technology has driven industry to combinatorial chemistry, peptide synthesis, and rational design strategies to overcome the difficulty of these choices. Nevertheless, despite the difficulty of integrating natural products into high-specificity, molecular biology-based, high-throughput screens, they remain the best source of complex, novel, bioactive compounds. Many examples of novel natural-product discoveries are contained in this review, but we are convinced that intelligent search strategies will uncover many more. The concept of the one strain/many compounds method for exploring new microbial secondary metabolites (405) continues to be very successful.
The high technology of modern molecular biology needs to be applied to understanding the growth and expression of metabolic potential by microorganisms and increased efforts must be made to continue to catalogue, classify, and describe microbial diversity. Consequently while these efforts continue, it is important that we actively protect biodiversity. These considerations finally lead us to an agenda of socioeconomic issues that go beyond strictly scientific matters that impact on the exploitation of biodiversity, which include ethical and legal issues related to sample collection and the impact of the Convention on Biological Diversity on business and company response (440); the concentration of biodiversity hot spots in developing countries and the expectations in those countries of advantageous bioprospecting deals; the effect of synthetic alternatives created in developed countries on such expectations, for example, the customized design of biocatalysts via gene shuffling and directed evolution (306); the conservation of microbial gene pools, and the respective arguments for in situ and ex situ conservation, and the access to and exchange of microorganisms in the interests of sustainable development in industrialized and developing nations (97); and assessment of the risk of transgenic organism release on indigenous biodiversity.
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