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

Ferredoxin/flavodoxin-NADP+ oxidoreductases, which conduct redox reactions, are crucial for various biological processes. However, their specific roles can vary between organisms and are not always easily deducible. In this study, the researchers identified a vital function for Bacillus subtilis YumC, a member of a unique group of bacterial FNRs that resemble thioredoxin reductase.

Employing targeted protein degradation, cytological profiling, metabolomics, and genetic complementation, the team demonstrated that YumC drives the transfer of electrons from NADPH to the isoprenoid biosynthesis pathway, either through ferredoxin (Fer) or via the flavodoxin YkuP. When YumC was disrupted, isoprenoid biosynthesis suffered, leading to a reduced level of undecaprenyl phosphate, a lipid carrier for peptidoglycan construction.

Eliminating YumC or ferredoxin in a deficient YkuP strain resulted in impaired peptidoglycan biosynthesis, activation of the sigmaM-dependent cell-wall stress response, and ultimately, cell death. Although an alternative pathway for isoprenoid biosynthesis, independent of electron-carrier proteins, can compensate for the degradation of Fer in a YkuP-deficient strain, it cannot replace the removal of YumC.

This evidence suggests that YumC is essential for other critical processes that may not rely solely on Fer and YkuP. The findings clarify the importance of YumC, elucidate the mechanism through which reducing power reaches isoprenoid biosynthesis in Bacillus subtilis, and highlight how redox systems' diverse roles in bacteria are contingent upon their metabolic context.