Living, cell-based bioelectronic devices are an emerging technology with broad applications in sensing, production, and remediation. These biotic-abiotic hybrids leverage one of biology’s key processes: electron transfer within and across the cellular membrane. As our understanding of electron transfer pathways expand, our ability to construct synthetic electron transfer pathways and engineer control over these reactions enable the creation of more efficient cell-material devices. One way to program electron transfer in microbes is to diversify the proteins that participate in these reactions (e.g., oxidoreductases) through protein engineering. However, successful enzyme engineering studies depend on appropriate assays to evaluate and characterize the desired variants. The Escherichia coli NADPH-dependent sulfite reductase is a heterododecameric complex that mediates one of the three known six-electron reductions in biological systems, catalyzing the reduction of sulfite to sulfide. Its higher order structure consists of an oxidative flavoprotein subunit and a reductase hemoprotein subunit that assemble in a unique asymmetrical stoichiometry to efficiently coordinate the large-volume electron transfer reaction. This oxidoreductase lends itself to numerous design opportunities due to (i) available crystal structures allowing rational design and (ii) essential catalytic activity that is crucial to E. coli metabolism in auxotrophic conditions, facilitating large-scale mutagenic library evaluation through a high-throughput growth selection. Herein, I describe my efforts in developing robust assays for studying engineered E. coli sulfite reductases. To enable recombinant expression of homogeneous protein, I modified an existing E. coli strain through a genetic deletion. I demonstrate that wild-type sulfite reductase can be easily purified in this strain by an affinity tag on the flavoprotein component without impacting oligomerization or catalytic function. I show that sulfite reductase activity can be monitored in vitro using an electrode and that this method presents an advantage over the traditional method when assessing activity in mutants. Additionally, I optimized a microplate-based endpoint assay that can be theoretically used to screen sulfite reductase mutants designed to accept electrons from other redox molecules beyond the native cofactor. This work supports future studies involving engineered E. coli sulfite reductase that may lead to the creation of new electron transfer biocomponents applicable to living bioelectronics.