We report our efforts to enable transition-metal catalysis in the presence of cellular debris, notably Escherichia coli cell free extracts and cell lysates. This challenging goal is hampered by the presence of thiols, mainly present in the form of glutathione (GSH), which poison precious metal catalysts. To overcome this, we evaluated a selection of oxidizing agents and electrophiles toward their potential to neutralize the detrimental effect of GSH on a Ir-based transfer hydrogenation catalyst. While the bare catalyst was severely inhibited by cellular debris, embedding the organometallic moiety within a host protein led to promising results in the presence of some neutralizing agents. In view of its complementary to natural enzymes, the asymmetric imine reductase based on the incorporation of a biotinylated iridium pianostool complex within streptavidin (Say) isoforms was selected as a model reaction. Compared to purified protein samples, we show that pretreatment of cell free extracts and cell lysates containing Say mutants with diamide affords up to >100 TON's and only a modest erosion of enantioselectivity.