Chemistry Seminar with Dr. Jennifer DuBois from Montana State University

Abstract: Iron is the quintessential biocatalytic metal, unleashing the growth-promoting power of O₂. Yet, O₂ is largely unavailable in many metabolically robust environments, including the anoxic interiors of wounds, tumors, and compost heaps, and the lumen of the gastrointestinal (GI) tract. We asked: how do the anaerobic species that thrive in these environments use metals to carry out reactions that canonically depend on Fe and O₂? We recently described a long-sought, O₂-independent mechanism by which dietary heme – at once a highly bioavailable iron source and cancer-promoting compound – is catabolized by widespread anaerobic species from GI tract consortia. At the heart of this mechanism is HmuS, a >1400 amino acid, monomeric de-chelatase that deconstructs heme to produce protoporphyrin IX and Fe(II). This enzyme is pervasive in the GI tracts of healthy humans, where the hmu pathway may serve as a primary entry point for heme-iron into the host-microbiome ecosystem. We propose a structure-based mechanism for this unusual reaction and describe the pathway’s possible implications for health.