Dianne K. Newman
Ph.D., 1997, Massachusetts Institute of Technology
Electron-transfer reactions are fundamental to metabolism. Whether an organism is autotrophic or heterotrophic, free living or an obligate parasite, every cell must solve the energy-generation problem to survive. At the cellular level, most of our knowledge of electron transfer comes from mechanistic studies of oxygenic photosynthesis and aerobic respiration in prokaryotic and eukaryotic systems. While we know in exquisite detail the structure and function of various membrane-bound proteins involved in electron-transfer processes (e.g., cytochrome c oxidase in mitochondria), we know far less about the electron-transfer agents of more ancient forms of metabolism. As geobiologists interested in the origin and evolution of the biochemical functions that sustain modern life, our work has focused on probing the co-evolution of metabolism with Earth's near-surface environments. Understanding how modern microorganisms with archaic metabolisms function is a step towards this end. Moreover, because many biological microenvironments are anaerobic, including those in most bacterial infections, this path of inquiry leads inexorably to insights about cellular electron-transfer mechanisms that potentially have profound biomedical implications.
Because rocks provide the primary record of ancient events and processes, our laboratory initially explored microbe-mineral interactions. In particular, we investigated how bacteria catalyze mineral formation, transformation, and dissolution, focusing on how these processes relate to cellular energy generation or membrane organization, and how they affect the geochemistry of their environment. For every pathway that we studied, we chose model organisms that we could genetically manipulate. Through a combination of classical genetic, biochemical, and molecular biological approaches, we identified the genes and gene products that controlled the processes of interest. For example, we discovered how bacteria use sediment-bound arsenate as a terminal electron acceptor in anaerobic respiration and convert it to arsenite, a more toxic and mobile form; how anoxygenic photosynthetic bacteria utilize ferrous iron [Fe(II)] as an electron donor in photosynthesis, thereby precipitating rust anaerobically; and how magnetotactic bacteria position the magnetosome, an organelle-like structure in which nanoparticles of magnetite are made. As our work progressed, however, it became increasingly clear that our findings transcended microbe-mineral interactions. Accordingly, our focus has shifted towards exploring more basic physiological questions that are relevant to diverse biological systems. Still, a geobiological perspective imbues our approach, compelling us to evaluate the functions of modern biomolecules in an evolutionary context.
We are currently exploring two major thematic areas:
I. The "light side": evolution of photosynthesis (focusing on how certain anoxygenic phototrophs utilize Fe(II) as an electron donor to power their metabolism, and determining the cellular function of 2-methylbacterial hopanoids—isoprenoids found in the membranes of both anoxygenic and oxygenic phototrophs, but whose molecular fossil derivatives have been used as biomarkers for the rise of oxygenic photosynthesis in the rock record).
II. The "dark side": physiological functions of redox active "secondary" metabolites (focusing on phenazine "antibiotics" produced by Pseudomonas aeruginosa PA14, an opportunistic pathogen that colonizes the lungs of individuals with the disease cystic fibrosis).