Implementation of a rapid microbial screening procedure for biotransformation activities.
A rapid and efficient microbial screening procedure was developed utilizing a 24-well plate format in conjunction with an automated liquid handling system and an HPLC. For the evaluation of this miniaturized and automated screening system, we selected the bioreduction of 6-bromo-beta-tetralone to 6-bromo-beta-tetralol. This procedure employed both yeast and rhodococci libraries, representing a culture collection comprised of several hundred strains, from which to screen for desirable bioconversion activity. Most of these strains had demonstrated bioreducing activity during previous screens to insure a "hit rate" as high as possible. The cultivation of microbes in the plate format was facile, time saving, and efficient compared to the standard method of screening utilizing larger volumes, such as test tubes or shake flasks. This improved method of screening for bioconversion activity, employing pre-selected microbial libraries based on microtiter plates and a fully roboticized analytical system, proved to rapidly yield valuable leads which compared advantageously with a more classical approach. A total of 192 yeast strains and 48 rhodococci strains were screened using this procedure. Analytical data revealed that 78% of the strains tested bioconverted the tetralone to the desired alcohol.
Stahl
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S
Department of Bioprocess R&D, Merck Research Laboratories, Rahway, NJ, USA.
Greasham
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R
Chartrain
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M