Extended Data Fig. 9. Theoretical evolutionary scenario of sulfite reductases.

The proposed route is based on the assumption that aSir, dSir and Fsr could have evolved from a common ancestor. The primordial sulfite reductase model corresponds to the elementary sulfite reductase core of the MtFsr structure. The different steps that led to the evolution of this progenitor to modern Fsr can be hypothesized based on its modular organization. In a straightforward and simple model, a ferredoxin with 2 × [4Fe‒4 S]-cluster could have been inserted into the elementary sulfite reductase module. Then an F₄₂₀H₂-oxidase with a ferredoxin domain (Fqo/FpoF-like) would have been fused to the N-terminus of the sulfite reductase domain containing the inserted ferredoxin. Some members of the Sir superfamily might have arisen from one of these steps¹⁸. Such a hypothesis is exemplified by the similarities between the quaternary organization of Fsr and DsrAB and the active site of Fsr and aSir.