In this work, recently published in the Journal of Biological Chemistry, we use a number of biochemical and structural analyses to show that a previously uncharacterised protein from Mycobacterium smegmatis acts as a flavin-sequestering protein that is required for survival during hypoxia. We show that this protein is a member of the flavin- and deazaflavin-dependent oxidoreductases (FDORs) and is distributed across mycobacterial species. X-ray crystallography revealed how FAD binds and showed no other substrate-binding cavities – consistent with its role as a flavin-sequestering protein. These findings present a new paradigm in mycobacterial adaptation to hypoxia.
This work was led by members of Greg Cook’s group (University of Otago/University of Auckland) and a collaboration with Trevor Rapson (CSIRO) and Chris Greening (Monash). Congratulations to all involved with this work.