Discovery, Dissection, Exploitation and Mimicry of Nature's Inorganic Chemistry to Secure the Future

The Metals in Biology Gordon Research Conference (MIB GRC) addresses long-standing, central challenges and emerging trends in the field of bioinorganic chemistry. The 2019 MIB GRC will focus on novel, complex transformations in natural product biosynthesis, complex metallocofactor assembly and function, metal trafficking relevant to infectious disease, deployment of metalloenzymes for energy and commercial applications, and elucidation of modern metallobiogeochemistry and how it evolved. A primary goal of the 2019 meeting will be to increase participation by scientists from underrepresented groups and ensure equitable gender representation among speakers and discussion leaders.

Metalloenzymes catalyze the most challenging and consequential chemical reactions on earth, including ATP-driven dinitrogen reduction and photochemical water oxidation. The complex clusters of redox-active transition metal ions and exogenous (in)organic ligands that support these reactions must be assembled/inserted into proteins by elegant biosynthetic machinery. Delineating the pathways for construction and the mechanisms of function of these elaborate multi-electron redox catalysts is a central challenge to the field of bioinorganic chemistry; analysis of how they arose on earth is fundamental to our understanding of our origins.

In addition to these central players in earth's element and energy economy, organisms have evolved an astounding array of metalloenzymes, powered by simple and complex metal cofactors, that promote reactions meeting specialized needs of diverse organisms in varied ecological niches. Some of these enzymes support basic metabolism and regulation, while others assemble Nature's astounding inventory of complex secondary metabolites, installing unusual functional groups that confer potent bioactivities. The direct deployment, engineering, and mimicry of these enzymes for research and commercial applications, another primary goal of bioinorganic chemists, holds great promise for society.

Most metalloproteins function only with a specific metal ion or cluster. This stringent metal specificity is one reason why cells must maintain concentrations within a relatively narrow range: too little of a trace metal can deprive essential metalloenzymes of their cofactors; too much can cause mismetallation of other biomolecules, blocking their functions. Cells and organisms balance uptake and efflux of each trace metal and control its distribution. Homeostasis is often antagonized by host or competing organisms that actively sequester (or, less commonly, induce overload of) essential metals. Mapping this complex metal-trafficking network, and exploiting it for disease therapy, are important goals of the field.

As sophisticated as Nature's catalysts are, they deploy only a small fraction of the periodic table. Abiological metals have surprising and useful bioactivities that have been leveraged for treatment of cancer, arthritis, and infectious diseases. In other cases, such metals are the basis for imaging diagnostics. When incorporated into proteins, these metals can enable reactions not represented among natural enzymes. Bioinorganic chemists continue to extract general principals underlying catalysis by metalloenzymes and marry them with the known chemistry of abiological metals to develop novel catalysts. Biomimetic and bioinspired chemistry is a vibrant focus of the field and provides underpinnings for innovation of new processes and deeper insight into Nature's elegant inorganic chemistry.