The ferredoxin/flavodoxin-NADP + oxidoreductase YumC is essential for isoprenoid and peptidoglycan biosynthesis in Bacillus subtilis.

Redox reactions mediated by ferredoxin/flavodoxin-NADP + oxidoreductases (FNRs) and their associated electron-carrier proteins, ferredoxins and flavodoxins, are essential in biology. Although the biochemical activities of these redox proteins are conserved, their precise physiological roles can differ among organisms and cannot be easily inferred. Here we have defined an essential role for Bacillus subtilis YumC, a member of a distinct group of bacterial FNRs that resemble thioredoxin reductase. We have used targeted protein degradation, cytological profiling, metabolomics, and genetic complementation to show that YumC catalyzes the transfer of electrons from NADPH, through ferredoxin (Fer) or through the flavodoxin YkuP, to the isoprenoid biosynthesis pathway, and specifically to the redox enzyme IspG. When YumC was degraded, isoprenoid biosynthesis was compromised, and the level of undecaprenyl phosphate, the isoprenoid lipid carrier for peptidoglycan building block translocation, was diminished. Degradation of YumC or of Fer in a Δ ykuP strain led to defective peptidoglycan biosynthesis, activation of the σ M -dependent cell-wall stress response, and lethality. The introduction into B. subtilis of an alternative pathway for isoprenoid biosynthesis that does not require input from electron-carrier proteins could complement the degradation of Fer in a Δ ykuP strain, but not the degradation of YumC. This finding indicates that YumC is required for other essential processes that do not necessarily involve Fer and YkuP. This work provides an explanation for why YumC is essential, reveals how reducing power is delivered to isoprenoid biosynthesis in B. subtilis, and illustrates how the varied roles of redox systems among bacteria depend upon metabolic context.