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Search and discovery strategies for biotechnology: The paradigm shift

Lookup NU author(s): Professor Alan Bull, Emeritus Professor Alan Ward, Professor Michael Goodfellow


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Profound changes are occurring in the strategies that biotechnology-based industries are deploying in the search for exploitable biology and to discover new products and develop new or improved processes. The advances that have been made in the past decade in areas such as combinatorial chemistry, combinatorial biosynthesis, metabolic pathway engineering, gene shuffling, and directed evolution of proteins have caused some companies to consider withdrawing from natural product screening. In this review we examine the paradigm shift from traditional biology to bioinformatics that is revolutionizing exploitable biology. We conclude that the reinvigorated means of detecting novel organisms, novel chemical structures, and novel biocatalytic activities will ensure that natural products will continue to be a primary resource for biotechnology. The paradigm shift has been driven by a convergence of complementary technologies, exemplified by DNA sequencing and amplification genome sequencing and annotation, proteome analysis and phenotypic inventorying, resulting in the establishment of huge databases that can be mined in order to generate useful knowledge such as the identity and characterization of organisms and the identity of biotechnology targets. Concurrently there have been major advances in understanding the extent of microbial diversity, how uncultured organisms might be grown, and how expression of the metabolic potential of microorganisms can be maximized. The integration of information from complementary databases presents a significant challenge. Such integration should facilitate answers to complex questions involving sequence, biochemical, physiological, taxonomic, and ecological information of the sort posed in exploitable biology. The paradigm shift which we discuss is not absolute in the sense that it will replace established microbiology; rather, it reinforces our view that innovative microbiology is essential for releasing the potential of microbial diversity for biotechnology penetration throughout industry Various of these issues are considered with reference to deep-sea microbiology and biotechnology.

Publication metadata

Author(s): Bull AT, Ward AC, Goodfellow M

Publication type: Review

Publication status: Published

Journal: Microbiology and Molecular Biology Reviews

Year: 2000

Volume: 64

Issue: 3

Pages: 573-606

ISSN (print): 1092-2172

ISSN (electronic): 1098-5557


DOI: 10.1128/MMBR.64.3.573-606.2000