Special Biochemistry Seminar

Summary

Many bacteria use the trace quantities of Hydrogen (H2) present in the atmosphere as an energy source for growth and survival. This globally significant process regulates the atmosphere's composition, enhances soil biodiversity, and drives primary production in extreme environments. Bacteria use enzymes called [NiFe]-hydrogenases to oxidise atmospheric H2. However, how these enzymes overcome the extraordinary catalytic challenge of oxidising picomolar levels of H2 in the presence of the catalytic poison O2 remained unknown. To resolve this, we determined the 1.52 Å Cryo-EM structure of the mycobacterial hydrogenase Huc and investigated its mechanism. Huc uses narrow hydrophobic gas channels to selectively bind atmospheric H2 at the expense of O2, while three [3Fe-4S] clusters modulate its properties so that atmospheric H2 oxidation is energetically feasible. The Huc catalytic subunits form an octameric 833 kDa complex around a membrane-associated stalk, which transports and reduces menaquinone a remarkable 94 Å from the membrane. This work provides a mechanistic basis for atmospheric H2 oxidation, uncovers a novel mode of energy coupling dependent on long-range quinone transport, and paves the way for developing H2 biosensors, and catalysts that oxidise H2 in ambient air.

Biography

Dr Rhys Grinter runs the Molecular Physiology of Microbial Pathogens (MP2) Lab in the Department of Microbiology at Monash University. He completed an honours degree in Biotechnology at Flinders University and received his PhD from the University of Glasgow. In 2015, he obtained a Sir Henry Wellcome Fellowship and returned from the UK to Australia to work on iron uptake by bacterial pathogens at Monash University. In 2021, he founded his lab and was awarded an NHMRC Investigator Grant to continue his work on iron piracy by bacterial pathogens. In addition to this work, he performs ARC-funded research into the structure and function of bacterial enzymes that oxidise atmospheric trace gases and discovering novel antibiotics to combat the antibiotic resistance crisis. The Grinter lab utilises current and emerging technologies to understand how microbes work. It harnesses this understanding to prevent disease and to develop enzymes and natural products as tools for biotechnology. It utilises diverse techniques across genomics, bioinformatics, molecular microbiology, biochemistry, and structural biology.