Search and discovery strategies for biotechnology: The paradigm shift

Profound changes are occurring in the strategies that biotechnology-based i ndustries are deploying in the search for exploitable biology and to discov er new products and develop new or improved processes. The advances that ha ve been made in the past decade in areas such as combinatorial chemistry, c ombinatorial biosynthesis, metabolic pathway engineering, gene shuffling, a nd directed evolution of proteins have caused some companies to consider wi thdrawing from natural product screening. In this review we examine the par adigm shift from traditional biology to bioinformatics that is revolutioniz ing exploitable biology. We conclude that the reinvigorated means of detect ing novel organisms, novel chemical structures, and novel biocatalytic acti vities will ensure that natural products will continue to be a primary reso urce for biotechnology. The paradigm shift has been driven by a convergence of complementary technologies, exemplified by DNA sequencing and amplifica tion genome sequencing and annotation, proteome analysis and phenotypic inv entorying, resulting in the establishment of huge databases that can be min ed in order to generate useful knowledge such as the identity and character ization of organisms and the identity of biotechnology targets. Concurrentl y there have been major advances in understanding the extent of microbial d iversity, how uncultured organisms might be grown, and how expression of th e metabolic potential of microorganisms can be maximized. The integration o f information from complementary databases presents a significant challenge . Such integration should facilitate answers to complex questions involving sequence, biochemical, physiological, taxonomic, and ecological informatio n of the sort posed in exploitable biology. The paradigm shift which we dis cuss is not absolute in the sense that it will replace established microbio logy; rather, it reinforces our view that innovative microbiology is essent ial for releasing the potential of microbial diversity for biotechnology pe netration throughout industry Various of these issues are considered with r eference to deep-sea microbiology and biotechnology.