In the particular selection described here, we hypothesized that we could improve GRMLR reduction of the intracellular form of Selenium, GS-Se-SG, by challenging the cells with 50mM selenite in liquid culture. The basis for this selection is to find GRLMR variants that reduce more bio-active intracellular Se (4+) into less available Se (0) at a greater rate, promoting a competitive advantage and thus generating selective pressure in favor of the host cell. As shown above, however, this initial hypothesis was not entirely correct, as we instead unexpectedly evolved an enzyme with decreased activity toward GS-Se-SG and improved activity toward SeO3 2-. A previous study demonstrated evolution of chromate reductase in a 96-well plate format to become a catalytically more efficient enzyme toward chromate . We opted to develop the selection method described here because it can accommodate much larger library sizes, with higher throughput and reduced labor. We additionally rationalized that a free-floating culture (as opposed to solid media) would prevent cells from depleting their local exterior selenite concentration, placing more selection emphasis on intracellular chemistry.