NfuA is a Fe-S carrier protein that has been shown to regenerate LipA’s sacrificial auxiliary [4Fe-4S] cluster thereby promoting multi-turnover production of lipoic acid, an essential sulfur-containing enzyme cofactor of aerobic metabolic enzymes. We use the amenable Thermosynechococcus elongatus (T. elongatus) to crystallographically elucidate the mechanism of Fe-S regeneration between LipA-NfuA. We also investigate the impact of introducing a non-native metal binding residue NfuA to shed light on its therapeutic implications.